Study of prevalence and clinical characterization of Fabry disease in a central northern region of Chile (2013–2023)

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Diagnosis combines clinical evaluation, biochemical testing and genetic analysis. Early initiation of enzyme replacement therapy (ERT) is crucial to prevent irreversible damage. In Chile, information on prevalence and clinical characteristics of FD is limited. The study aimed to estimate the prevalence of FD and characterize patients in the Coquimbo Region of Chile, between 2013 and 2023. Methods Descriptive cross-sectional study of 69 patients with FD. The following variables were recorded in an anonymized clinical questionnaire: sex, age, residence, health insurance, start of therapy, type of ERT, chronic medication, type of clinical manifestation and type of genetic mutation. Descriptive statistics and correlation tests were used for the analysis. Prevalence was calculated on the regional population average projected by the National Institute of Statistics (INE) for the period 2013–2023. Results The regional prevalence rate was 8.44 per 100,000 inhabitants (95% CI: 6.44–10.43), with a particularly high value in the commune of Coquimbo (22.45 per 100,000 inhabitants). The majority were women (58.0%), with a mean age of 35.8 years. Ninety-four percent had the classical form of FS, and 95.7% carried the P259R mutation. ERT was initiated in 2016 for 58% of patients, and 55.1% received agalsidase alfa. Peripheral nervous system (PNS) involvement was present in 71.0% and renal involvement in 39.1%. 46.4% used complementary drugs, mostly analgesics, antihypertensives and antineuropathics, whose consumption increases with age. The older the patient, the greater the number of affected systems. Those with PNS involvement were younger. Conclusions The Coquimbo Region has the highest recorded prevalence of FD in Chile, concentrated in the commune of Coquimbo. The age of entry into treatment significantly influences both the number of affected systems and the chronic use of drugs. The high frequency of the P259R mutation suggests the need for genetic studies to explore possible common origins and ethnic factors that influence the clinical expression of the FD. A specialized FD care center is a strength for conducting further research on the disease. Fabry Disease genetic diseases inborn prevalence cross-sectional studies Figures Figure 1 Introduction Fabry disease (FD), also known as Anderson-Fabry disease, is a lysosomal disease caused by a genetic disorder linked to the X chromosome, produced by mutations in the GLA gene. These mutations cause a deficiency or absence of the lysosomal enzyme alpha-galactosidase A, leading to the progressive accumulation of globotriaosylceramide (Gb3 or GL-3) and other glycosphingolipids in the lysosomes. It is a rare or uncommon, systemic disease whose pathological process begins at an early stage, even during fetal development. However, most patients remain asymptomatic during the first years of life. The clinical manifestations of FD are broad and heterogeneous, and many of them can present as common symptoms. Among the most common symptoms are skin lesions, particularly angiokeratomas, which are present in many cases. Cardiac involvement is observed in approximately 40 to 60% of patients, with cardiac muscle hypertrophy being one characteristic manifestation. Kidney disease is also common, with microalbuminuria, proteinuria and progressive deterioration of kidney function. From a neurological point of view, acroparesthesia as a manifestation of small fiber neuropathy are frequent. Ophthalmologically, whorled cornea, vascular tortuosity, and cataracts may be observed. In addition, neuro-otological manifestations have been described, such as progressive or sudden hearing loss. There is, as well, the involvement of the brainstem, central nervous system, or peripheral nervous system. Gastrointestinal disorders affect between 50 and 60% of patients, and bone and pulmonary complications may also occur [ 1 , 2 , 3 ]. FD occurs in two main forms: the classic form and the non-classic form. The classic form, which has an early onset, is usually more severe and is caused by a complete or almost complete deficiency of the enzyme alpha-galactosidase A (activity < 3%). It generally begins in childhood or adolescence and predominantly affects men, although it can also manifest in female carriers. On the other hand, the non-classical form (or late variant) has a later onset, usually presents a milder phenotype, and has variable clinical progression. In these cases, residual enzyme activity is higher (usually < 30% in men). Patients may predominantly develop cardiac manifestations (such as cardiomyopathy), renal failure, or cerebrovascular accidents [ 3 ]. The diagnosis of FD is based on the evaluation of clinical signs and symptoms, which can be nonspecific and shared with other pathologies, making it difficult to confirm based on clinical criteria alone. For this reason, biochemical diagnosis is used, which includes measuring the enzymatic activity of alpha-galactosidase A in plasma or leukocytes, and genetic analysis to identify mutations in the GLA gene. In addition, the quantification of globotriaosylceramide (Gb3) in plasma and urine is used as a biomarker of lipid accumulation, useful both for diagnostic confirmation and for monitoring response to treatment [ 1 ]. Specific treatment of FD is based primarily on permanent enzyme replacement therapy (ERT) using agalsidase alfa or beta. Clinical evidence has shown that the best results (including prevention of irreversible damage) are obtained when ERT is started early and in a timely manner. In addition, therapy with pharmacological chaperones, specifically oral migalastat, has been shown to be an effective and safe alternative in patients who meet the established therapeutic criteria. On the other hand, many patients require supportive treatments or adjuvant therapies, which must be individualized according to clinical symptoms and the degree of involvement of the different organs and systems affected [ 4 , 5 ]. Various studies worldwide have reported variations in prevalence, which depend on factors such as the methodology used, the population analyzed, and the type of diagnosis used. For example, in 2019, the prevalence was estimated to be 1 in 117,000 live births in Australia [ 6 ]. However, more recent research incorporating neonatal screening, genetic sequencing techniques, and the use of biomarkers—in addition to measuring enzyme activity—has revealed higher prevalences. In this regard, analysis of databases of pathogenic variants of the GLA gene in men and women has shown a population frequency of 1 in 3,225 people in the population studied, with a higher prevalence in women [ 7 ]. These findings suggest an upward trend in the prevalence of FD and reinforce the hypothesis that the disease continues to be underdiagnosed. Knowing the prevalence and distribution of FD is essential to promote early detection, optimize clinical care, and properly guide public health policies. In this context, the Chilean Ministry of Health has established, since 2016, a protocol that provides specific guidelines for the entire network of healthcare providers who treat patients with FD. This document standardizes the diagnostic procedure, inclusion criteria, clinical management, and administration of ERT [ 8 ]. In Chile, the characterization and prevalence of FD are still not precisely known. The only available figures come from the National Health Fund (FONASA) database, which records 139 beneficiaries with financial coverage for FD [ 9 ]. It is noteworthy that almost half of these patients are concentrated in the north-central part of the country, especially in the Coquimbo Region, where they are treated by a specialized multidisciplinary team at the San Pablo de Coquimbo Hospital. For this reason, the present study aims to establish the prevalence and characterization of Fabry disease in the Coquimbo Region of Chile during the period 2013 to 2023. Methods A descriptive cross-sectional study was conducted to determine the prevalence and characterization of FD in the Coquimbo Region between 2013 and 2023. The sample included 69 patients with a confirmed diagnosis of FD, who received treatment and clinical follow-up at the San Pablo Hospital in Coquimbo, the regional referral center for this pathology, in accordance with the guidelines established by the Chilean Ministry of Health [ 8 ]. Of the 69 patients diagnosed, 6 died during the study period. Context: Geographical, sociodemographic, and health system description of the Coquimbo Region. The Coquimbo Region is in north-central Chile, between 29°02′ and 32°16′ south latitude and from 69°49′ west longitude to the Pacific Ocean (Fig. 1, left side). Its capital is the city of La Serena, and it is subdivided into three provinces: Elqui (6 municipalities), Limarí (5 municipalities), and Choapa (4 municipalities) (Fig. 1). According to data from the 2024 Census [ 10 ], the regional population is 832,864, distributed mainly in the province of Elqui (562,457), followed by Limarí (178,057) and Choapa (92,350). Eighty-one-point two percent of the population resides in urban areas, while 18.8% live in rural areas [ 11 ]. In terms of social indicators, 7.9% of the regional population lived in poverty in 2022, a figure higher than the national average (6.5%). The employment rate was 64% for men and 40.9% for women [ 12 ]. Chile's healthcare system is mixed, consisting of a public insurer (FONASA), which covers approximately 77% of the national population [ 13 ], and private insurers grouped together in the Health Insurance Institutions (ISAPRE), in addition to the Armed Forces' healthcare system. In 2015, Law No. 20,850 was enacted, establishing a financial protection system for high-cost diagnoses and treatments, applicable to beneficiaries of all social security schemes and financed by FONASA [ 14 ]. The health conditions covered by this law include FD. The Coquimbo Region has a public healthcare network organized into different levels of complexity. It has three high-complexity hospitals located in the most populated municipalities: Coquimbo, La Serena, and Ovalle; a medium-complexity hospital in the municipality of Illapel; and five low-complexity or community facilities in Andacollo, Combarbalá, Los Vilos, Salamanca, and Vicuña. In addition, the public primary healthcare system in the region consists of 358 facilities offering different levels of care and 26 emergency services distributed throughout the region [ 15 ]. Health care of patients with FD: Suspicion, diagnosis, treatment, and follow-up In the Coquimbo Region, the diagnosis and treatment of FD is centralized exclusively at the San Pablo Hospital in Coquimbo, the only facility in the region that has a neurology department and the Multidisciplinary Team for the Study and Treatment of Fabry Disease (EMETEF). Patients with suspected or confirmed FD can access the Ministry of Health public financial protection system for high-cost diagnoses and treatments, regardless of whether they are affiliated with the public (FONASA) or private health system, whose access is subject to evaluation and confirmation by an accredited committee of experts. There are two main ways to enter this system. The first is the diagnostic suspicion modality, aimed at patients with a well-founded suspicion of FD, usually formulated by medical specialists such as neurologists, internists, geneticists, or pediatricians. In men, the diagnosis is confirmed by measuring the enzymatic activity of alpha-galactosidase A in leukocytes, supplemented by molecular genetic analysis. In women, due to phenotypic variability and the possibility of normal enzyme activity, molecular genetic testing is required for diagnostic confirmation. The second is the therapeutic modality, which is aimed at patients with a previously confirmed diagnosis who require second-line treatment or treatment with greater therapeutic complexity. Standard treatment consists of ERT with agalsidase alfa or agalsidase beta, which must be administered by authorized providers and is covered by Law No. 20,850 [ 8 ]. Participants, instruments, ethical aspects, data collection and analysis The study included all 69 people diagnosed with FD in the Coquimbo Region between 2013 and 2023 who received treatment at the San Pablo Hospital in Coquimbo. For data collection, a questionnaire was designed using the Google Forms platform (Google LLC, Mountain View, CA, USA), without including fields that would allow the personal identification of patients, to guarantee confidentiality. The instrument was designed to be completed by the treating physician or a member of EMETEF and included instructions for its application and data recording. The study protocol was approved by the Scientific Ethics Committee of the Faculty of Medicine of the Catholic University of the North, under Resolution No. 56/2023. Institutional authorization was also obtained from the San Pablo Hospital in Coquimbo, the healthcare center where all patients with FD in the region are treated and whose clinical records are kept. The questionnaire was answered using information contained in clinical records and hospital files. The variables collected included: sex, age, municipality of residence, type of health insurance, year of initiation of therapy, type of enzyme replacement therapy, use of chronic medications, type of clinical manifestation, and type of genetic mutation. The analysis of clinical manifestations focused on the main organs or systems affected: peripheral nervous system (PNS), renal system (RF), heart (HT), and central nervous system (CNS). Patients were classified according to the type of mutation, specifically identifying the presence or absence of the classic mutation of the disease. The prevalence of FD was estimated considering the 69 confirmed cases throughout the study period, without excluding deceased patients. The denominator used was the average regional population projection for the years 2013 to 2023, according to the National Institute of Statistics (INE) data [ 16 ], and the 95% confidence interval was calculated. For statistical analysis, contingency tables and the chi-square test (p < 0.05) were used to evaluate associations between sex and type of condition, as well as between sex and chronic medication use. The comparison between independent groups—such as age, presence of specific clinical manifestations, and use of chronic medications—was performed using the Student's t-test, the nonparametric Mann-Whitney U test, or Welch's t-test in cases where the assumption of homogeneity of variances was not met (p < 0.05). In addition, a nonparametric correlation (Spearman's Rho) was performed between the number of affected systems and the number of chronic medications consumed with age. Data processing and analysis were performed using JASP software version 0.18.3.0 and IBM SPSS Statistics version 26. Results Ninety-four percent (94%) of the patients included in the study had the classic form of FD, and 92.8% carried the P259R mutation. The demographic and clinical characteristics of the 69 patients are detailed in Table 1. Fifty-eight percent were women, with a female-to-male ratio of 1.4:1. The age of the participants ranged from 6 to 73 years, with a mean of 35.8 ± 18.67 years; when broken down by sex, the mean age was 38.5 ± 19.75 years in women and 32.0 ± 16.34 years in men. 86.2 percent of patients were over 14 years of age. In terms of geographical distribution, the majority resided in the province of Elqui (92.8%), specifically in the municipality of Coquimbo (81.2%). See Figure 1, right side. Concerning the type of health insurance, 97% were affiliated with the public system and only 3% had private insurance. Regarding ERT, 58.0% of patients began treatment in 2016, coinciding with the entry into force of Law No. 20,850. However, by 2023, 10.1% had not yet begun ERT. Agalsidase alfa was used in 55.1% of cases, and among patients who received ERT, 61.3% were treated with agalsidase alfa and 38.7% with agalsidase beta. About the clinical manifestations and multisystem involvement characteristic of FD, 71.0% of patients had PNS involvement, followed by RF involvement in 39.1%. No statistically significant differences were observed between sex and type of involvement. In addition to enzyme treatment, 46.4% of patients used complementary medications due to the type of involvement and the presence of chronic comorbidities, and in this group, women accounted for 69.5%. The most used drugs were analgesics (47.8%), antihypertensives (42.0%), and anti-neuropathic (27.5%). Table 1. Characterization of patients with Fabry disease, Coquimbo Region, Chile, 2013–2023. Variable Category N % Sex Men 29 42.0% Women 40 58.0% Age range of therapy initiation 0 to 14 12 17.4% 15 to 29 17 24.6% 30 to 44 19 27.5% 45 to 59 11 15.9% 60 to 74 10 14.5% 75 and over 0 0.0% Death rate 6 7.3% Type of mutation P259R 66 95.7% RPCF4 2 2.9% pW81X 1 1.4% Province Elqui 64 92.8% Limarí 5 7.2% Choapa 0 0.0% Type of insurance Public (FONASA) 67 97.1% Private 2 2.9% Enzyme replacement therapy Agalsidasa alfa 38 55.1% Agalsidasa beta 24 34.8% Without ERT 7 10.1% Type of clinic involvement Peripheral Nervous System (PNS) 49 71.0% Renal System (RF) 27 39.1% Heart (HT) 26 37.7% Central Nervous System (CNS) 10 14.5% Type of medication for chronic use Analgesics 33 47.8% Antihypertensives 29 42.0% Antineuropathics 19 27.5% Hypolipidemic agents 16 23.2% Antiplatelet agents 14 20.3% Antiarrhythmics 7 10.1% Anticoagulants 4 5.8% Antivertiginants 2 2.9% Source: own elaboration The prevalence rates of FD in the Coquimbo Region are presented in Table 2. The overall prevalence was 8.44 per 100,000 inhabitants (95% CI: 6.44–10.43), with a higher rate observed in women compared to men. Among the three provinces in the region, Elqui had the highest prevalence, particularly in the commune of Coquimbo, with a rate of 22.45 per 100,000 inhabitants (95% CI: 16.57–28.33), the highest in the entire territory analyzed. In terms of distribution by age group, the highest prevalence rates were observed in the 30–44 and 60–74 age ranges, with similar values between the two. Table 2: Prevalence of Fabry disease in the Coquimbo Region, Chile, 2013–2023. Variable Category Population Number of cases Rate per 100000 inhabitants C.I. 95% Lower Upper Sex Men 400573 29 7.23 4.60 9.87 Women 416895 40 9.59 6.62 12.56 Age range of therapy initiation 0 to 14 169436 12 7.08 3.07 11.08 15 to 29 179244 17 9.48 4.97 13.99 30 to 44 173370 19 10.95 6.03 15.88 45 to 59 152399 11 7.21 2.95 11.48 60 to 74 99182 10 10.08 3.83 16.33 75 and over 43837 0 Elqui Province 542112 64 11.8 8.91 14.69 Commune Coquimbo 249437 56 22.45 16.57 28.33 La Serena 242699 4 1.64 0.03 3.26 Vicuña 29261 1 3.41 n.c. n.c. Andacollo 11698 1 8.54 n.c. n.c. Paihuano 4631 2 43.18 n.c. n.c. La Higuera 4386 0 0 0 0 Limarí Province 181813 5 2.75 0.33 5.16 Commune Ovalle 119409 4 3.34 0.06 6.63 Monte Patria 32266 0 0 0 0 Combarbalá 13807 0 0 0 0 Punitaqui 11961 1 8.36 n.c. n.c. Río Hurtado 4370 0 0 0 0 Choapa Province 93543 0 0 0 0 Total Coquimbo Region 817468 69 8.44 6.44 10.43 n.c. not calculable. Source: own elaboration Table 3 presents a comparison of ages at ERT initiation according to the presence or absence of clinical manifestations and medicines for chronic use. It was observed that patients with FD who presented some type of clinical condition had a significantly higher average age of therapy initiation than those without clinical manifestations. When analyzing the different types of conditions, it was found that patients with PNS involvement were significantly younger than the other groups, with an average age of 39.2 ± 17.6 years (p = 0.015). Likewise, chronic consumption of medications for the relief of other types of symptoms also showed differences in terms of age, except for anti-neuropathic and antivertiginous drugs. In general, those consuming this type of medication were older at the time of starting treatment. Table 3: Clinical involvement according to age at the start of ERT in patients with FD, Coquimbo Region, Chile, 2013-2023. Affected System With affectation No affectation Difference in age (mean) according to affected system Age of therapy initiation (years) Age of therapy initiation (years) Mean S.D. Median Mean S.D. Median 1 p PNS 39.2 17.6 40 27.2 19.2 26 0.015 RF 49.7 15.7 51 26.7 14.7 26 <0.001 HT 52.8 13 52.5 25.4 13.5 26 <0,001 CNS 52.8 12 52 32.8 18.2 30 0.001 Type of Medication Consumption No consumption Difference in age (mean or median) by use of medications Age of therapy initiation (years) Age of therapy initiation (years) Mean S.D. Median Mean S.D. Median 1 p Analgesics 41.6 18.9 43 30.3 17.2 28 0.012 Antihypertensives 51.5 12.9 52 24.3 13.2 24 <0.001 Antineuropathics 39.4 19 43 34.3 18.7 30 0.324 Hypolipidemic agents 58.1 10 59 29 15.2 27 <0.001 Anti-aggregants 58.4 10.5 59 30 15.8 28 <0.001 Antiarrhythmics 61.1 7.7 60 32.9 17.5 30 <0.001 2 Anticoagulants 66.7 6.7 67 33.8 17.6 31 <0.001 Antivertiginous 53 2.8 53 35.2 18.8 32 0.191 3 ERT: Enzyme Replacement Therapy; PNS: Peripheral Nervous System; RF: Renal System; HT: Heart; CNS: Central Nervous System; 1 Student´s Test; 2 Welch's t-test; 3 Mann-Whitney U test. Source: own elaboration. Table 4 shows the correlation indices between the number of systems affected and the number of chronic medications with the age of treatment onset. It can be observed that age has a significant influence on both the number of systems affected and the number of chronic medications consumed by patients. Table 4: Correlation between affected systems and chronic medications at the beginning of treatment, Coquimbo Region, Chile, 2013-2023. Variable Spearman´s Rho p value Number of systems affected - age 0.68 <0.001 Number of drugs of chronic use - age 0.747 <0.001 Source: own elaboration Discussion The prevalence observed in this study was 8.44 per 100,000 inhabitants in the Coquimbo Region, an elevated frequency considering that almost half of the cases registered in the country are concentrated in this region. This rate far exceeds those reported in various international studies, where the prevalence of FD varies between 1 per 40,000 and 140,000 inhabitants [ 17 ]. Similarly, prevalences ranging from 0.015 to 0.85 per 100,000 inhabitants have been reported, which may underestimate the true magnitude of the disease, as neonatal screening studies have revealed significantly higher figures [ 1 ]. Along these lines, a prevalence at birth of 1.25 per 100,000 inhabitants has been estimated in Australia and some European countries, although this could also be underestimated due to the variability in the life expectancy of patients with FD [ 18 ]. Although EF is classified as a rare or low-frequency pathology, its occurrence in the Coquimbo Region is of special interest, as evidenced by the findings of this study. An outstanding characteristic is the age distribution of the patients: approximately 46% are under 30 years of age, and the average age is slightly lower in men than in women, which agrees with what has been reported in several previous publications [ 19 , 20 , 21 ]. Regarding sex, this study found a higher prevalence of FD in women than in men, which contrasts with most internationally published studies. Previous studies, both in populations with chronic kidney disease (CKD) with and without dialysis and in neonatal screening programs, report a higher frequency of FD in males than in females, with high variability, being the prevalences much higher in places where neonatal screening is performed [ 22 , 23 , 24 ]. These differences can be explained by the genetic basis of the disease, which is linked to the X chromosome. In men, who have a single X chromosome, clinical manifestations tend to appear earlier, with greater severity and accelerated progression. In women, however, the clinical presentation is more heterogeneous, with frequently subtle symptoms, later onset, greater survival, and variability in severity, attributable to random inactivation of the X chromosome. This can result in both mild and severe phenotypes, depending on the degree of expression of the mutated allele of the GLA gene, which is responsible for encoding the enzyme alpha-galactosidase A. As a result, women tend to have higher enzyme levels and lower concentrations of liso-Gb3 compared to men, which makes early diagnosis difficult [ 25 , 26 , 27 ]. In addition, many women are diagnosed as asymptomatic carriers after family screening, which may have contributed to finding a higher proportion of female cases. The finding of a higher prevalence of FD in women in this study population suggests the existence of particular factors in the Coquimbo Region that could influence phenotypic expression, or the diagnostic strategies implemented. This result highlights the need for further regional genetic, epidemiological, and clinical studies to better understand this pattern and its implications for the detection and management of the disease. The high prevalence of FD in the province of Elqui accounts for approximately 43% of all cases recorded nationwide, with most patients concentrated in the commune of Coquimbo. It has been documented that the prevalence of FD can vary significantly depending on specific mutations and predominant genetic patterns in different populations and geographical regions [ 28 , 29 ]. In this study, over 90% of patients have the P259R mutation, suggesting the possible existence of a founder effect. Consequently, it is pertinent to investigate the origin and age of this mutation through advanced genotyping studies and identification of shared haplotypes. These analyses would make it possible to determine the degree of consanguinity among the cases reported in the province, as well as to evaluate the possible influence of minority ethnic components that could be modulating the genomic architecture and clinical manifestations of the disease [ 29 , 30 ]. Furthermore, many of these patients are enrolled in the public health system, suggesting a less favorable socioeconomic situation. This geographic and socioeconomic distribution reinforces the congenital and rare nature of this metabolic disease and has prompted the implementation of a specialized regional multidisciplinary team for its study, diagnosis, and treatment. The existence of a specialized and multidisciplinary center for the care of FD at the Hospital San Pablo de Coquimbo is in line with the recommendations of experts in Latin America, who emphasize the need to strengthen the capacities of the health system for the timely diagnosis, comprehensive treatment and continuous follow-up of patients. Likewise, this type of initiative is consistent with policies that promote the financing of medication and comprehensive care for rare diseases [ 31 ]. Concerning ERT, no differences were observed in the frequency of use between agalsidase alfa and agalsidase beta. This is probably because, once diagnosed with CF and the therapeutic requirement established, patients are randomly assigned to one or the other drug by FONASA. Both treatments have demonstrated comparable efficacy, with no significant differences in clinical manifestations, even when administered at different doses or frequencies. Likewise, there has been no evidence of a differential impact on long-term mortality between the two formulations [ 32 , 33 ]. It should be noted that some patients diagnosed with FD did not receive enzyme replacement therapy, which could be explained by the absence of symptoms at the time of diagnosis, especially in pediatric patients who did not yet meet the criteria established in the protocol [ 8 ]. However, clinical guidelines recommend starting ERT early, even before the onset of irreversible organ damage, with the aim of modifying the natural course of the disease, relieving pain, and improving quality of life. Several studies have shown that timely initiation of ERT can normalize plasma globotriaosylceramide (GL-3) levels, improve gastrointestinal symptoms, and reduce the incidence of renal and cardiac complications [ 34 , 35 ]. This is consistent with the findings of the present study, which indicate that the older the age at diagnosis, the greater the number of systems affected in patients. Given the multi-organ nature of FD, in addition to ERT, patients may require chronic use of one or more symptomatic medications. In Chile, these drugs can be provided free of charge through FONASA, or they may represent an out-of-pocket expense for the patient. In this study, it was observed that 46.4% of patients received additional pharmacological treatment, with analgesics being the most frequently used. This finding is probably related to the high prevalence of neuropathic pain, one of the characteristic and initial symptoms of FD. The low frequency of use of other chronic medications could be explained by the effectiveness of ERT in reducing or attenuating the signs and symptoms associated with the disease [ 33 ]. Likewise, greater use of complementary medications was observed as the age of the patients increased. In the analysis of the different types of systemic involvement in patients with FD, it was observed that those with PNS involvement had a significantly lower average age (39.2 years) compared to patients with RF, HT, and CNS involvement, whose average ages were higher. Similarly, people who used antineuropathic drugs also belonged to the younger age group, with no significant differences in age compared to those who did not receive such medication, and the effect size was small. This finding is consistent with the literature, which indicates that one of the first clinical manifestations of FD—often from childhood or adolescence—is acroparesthesia and Fabry neuropathic crises, characterized by acute neuropathic pain with a burning, stinging, or tingling sensation that can radiate to the distal extremities or other body regions [ 4 , 36 ]. In relation to CKD, its association with advanced age is widely recognized [ 37 ], which was corroborated in this study population. It has been reported that patients with FD may begin to show clinically relevant renal impairment —including cases requiring dialysis replacement therapy— from the age of 30, with progression intensifying between the ages of 40 and 50 [ 38 , 39 ]. This pattern reinforces the relationship observed between older age and renal involvement in the patients studied. Similarly, heart manifestations (HT), such as left ventricular hypertrophy or hypertrophic cardiomyopathy, tend to occur at more advanced stages, generally after age 30, and are associated with higher cardiac morbidity and mortality [ 40 , 41 ]. On the other hand, CNS involvement has also been linked to older ages, with symptoms ranging from headaches and dizziness to severe manifestations such as neuro-otological disorders or cerebrovascular events [ 42 , 43 ]. The main strength of the study is the minimal probability of patient loss, since all patients, both from public and private centers, are registered in the program and were included in the study. All diagnoses were validated, and data was even available for six deaths during the period. The only source of possible losses may be people who have moved out of the region or who are awaiting evaluation by a specialist. A second limitation of the study is that, with the method used, it is not possible to calculate confidence intervals for prevalence rates in municipalities with small populations, where 1 or 2 cases result in high rates with confidence intervals ranging from negative values. Finally, there is a limitation in the recording of patient age, since it is not the age of symptom onset, but rather the age at which each patient enters the program and begins enzyme replacement therapy. Conclusions The prevalence of FD in north-central Chile is the highest recorded nationally and internationally, with a significant concentration of cases in the municipality of Coquimbo, suggesting consanguinity. Unlike what has been reported in the international literature, in this region the disease predominantly affects women. The age of treatment initiation significantly influences both the number of systems affected and the number of chronic medications consumed by patients, emphasizing the need for early diagnosis through screening and recommending genetic counseling for already identified patients. The findings open the possibility of conducting more in-depth research on the genomic representation of this population, with the aim of identifying possible common origins and ethnic components that may influence the clinical expression and symptoms of FD. The region has a strategic advantage for this type of study, as it has a specialized, multidisciplinary center for FD at the San Pablo Hospital in Coquimbo, which serves as a regional reference for the diagnosis, treatment, and follow-up of this disease. Abbreviations CKD: Chronic kidney disease CNS: Central nervous system EMETEF: Multidisciplinary Team for the Study and Treatment of Fabry Disease ERT: Enzyme replacement therapy FD: Fabry disease FONASA: National Health Fund Gb3: Globotriaosylceramide HT: Heart INE: National Institute of Statistics ISAPRE: Private Health Insurance Institutions PNS: Peripheral nervous system RF: Renal system Declarations Ethics approval and consent to participate This study was approved by the Scientific Ethics Committee of the Faculty of Medicine of the Universidad Católica del Norte (Res. CECFAMED-UCN REV N°56/2023). Consent for publication Not applicable. Availability of data and materials The study database may be made available upon request to the corresponding author. Competing interests The authors declare that they have no conflicts of interest. Funding The authors did not receive funding from any organization for the presented research. The study was the thesis of the main author, to obtain the degree of Master in Public Health. Authors' contributions SR, FM and MC-M conceptualized and designed the study, FM, BC and SR collected the data, SR and MC-M did the methodology, MC-M and MR-S analyzed and interpreted the data, MC-M and SR drafted and wrote the final manuscript, MR-S and MC-M reviewed and edited the manuscript. All authors read and approved the final version of the manuscript. Acknowledgments To Juan Correa Parra, geographer, for designing the map (Figure 1). To the Multidisciplinary Team for the Study and Treatment of Fabry Disease of Coquimbo Hospital. References Germain DP. Fabry disease. Orphanet J Rare Dis. 2010;5(30):1–49. https://doi.org/10.1186/1750-1172-5-30 . Wanner C, Arad M, Baron R, Burlina A, Elliott PM, Feldt-Rasmussen U, et al. European expert consensus statement on therapeutic goals in Fabry disease. Mol Genet Metab. 2018;124(3):189–203. https://doi.org/10.1016/j.ymgme.2018.06.004 . Michaud M, Mauhin W, Belmatoug N, Garnotel R, Bedreddine N, Catros F, et al. When and how to diagnose Fabry disease in clinical pratice. Am J Med Sci. 2020;360(6):641–9. https://doi.org/10.1016/j.amjms.2020.07.011 . Politei JM, Bouhassira D, Germain DP, Goizet C, Guerrero-Sola A, Hilz MJ, et al. Pain in Fabry disease: Practical recommendations for diagnosis and treatment. CNS Neurosci Ther. 2016;22(7):568–76. https://doi.org/10.1111/cns.12542 . Nowicki M, Bazan-Socha S, Błażejewska-Hyżorek B, Kłopotowski MM, Komar M, Kusztal MA, et al. A review and recommendations for oral chaperone therapy in adult patients with Fabry disease. Orphanet J Rare Dis. 2024;19(1):1–13. https://doi.org/10.1186/s13023-024-03028-w . Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA. 1999;281(3):249–54. https://doi.org/10.1001/jama.281.3.249 . Kermond-Marino A, Weng A, Xi Zhang SK, Tran Z, Huang M, Savige J. Population frequency of undiagnosed Fabry disease in the general population. Kidney Int Rep. 2023;8(7):1373–9. https://doi.org/10.1016/j.ekir.2023.04.009 . Ministerio de, Salud. Jul. Protocolo 2019 diagnóstico y tratamiento basado en agalsidasa para personas con enfermedad de Fabry. https://www.minsal.cl/wp-content/uploads/2019/07/8.-10072019-Protocolo-LRS-Fabry-Agalsidasa_FINAL.pdf . Accessed 7 2025. Fondo Nacional de Salud. Ley Ricarte Soto. In: Serie de tableros interactivos. https://public.tableau.com/views/BeneficiariosLRS/ReporteLRS?showVizHome=no . Accessed 28 May 2025. Instituto Nacional de Estadísticas. Censo 2024. https://censo2024.ine.gob.cl/ . Accessed 23 Jun 2025. Instituto Nacional de Estadísticas. Censo de Población y Vivienda 2017. https://www.ine.gob.cl/estadisticas/sociales/censos-de-poblacion-y-vivienda . Accessed 23 Jun 2025. Accessed 23 Jun 2025. Ministerio de Desarrollo Social y Familia. Encuesta CASEN. In: Encuesta de Caracterización Socioeconómica Nacional. 2022. https://observatorio.ministeriodesarrollosocial.gob.cl/encuesta-casen . Accessed 23 Apr 2025. Fondo Nacional de Salud. Datos abiertos FONASA. https://www.fonasa.cl/sites/fonasa/datos-abiertos . Accessed 23 Apr 2025. Ministerio deS. 2015. Ley 20850 Crea un sistema de protección financiera para diagnósticos y tratamientos de alto costo y rinde homenaje póstumo a don Luis Ricarte Soto Gallegos. https://www.bcn.cl/leychile/navegar?org=&idNorma=1078148 . Accessed 23 Apr 2025. Servicio de Salud Coquimbo. Red Asistencial Pública de la Región de Coquimbo. https://sscoquimbo.redsalud.gob.cl/red-asistencial-publica/ . Accessed 17 May 2024. Instituto Nacional de Estadísticas. Proyecciones de población. https://www.ine.gob.cl/estadisticas/sociales/demografia-y-vitales/proyecciones-de-poblacion . Accessed 17 May 2024. Gilchrist M, Casanova F, Tyrrell JS, Cannon S, Wood AR, Fife N, et al. Prevalence of Fabry disease-causing variants in the UK Biobank. J Med Genet. 2023;60(4):391–6. https://doi.org/10.1136/jmg-2022-108523 . Koto Y, Sakai N, Lee Y, Kakee N, Matsuda J, Tsuboi K, et al. Prevalence of patients with lysosomal storage disorders and peroxisomal disorders: A nationwide survey in Japan. Mol Genet Metab [Internet]. 2021;133(3):277–88. https://doi.org/10.1016/j.ymgme.2021.05.004 . Arends M, Wanner C, Hughes D, Mehta A, Oder D, Watkinson OT, et al. Characterization of classical and nonclassical fabry disease: A multicenter study. J Am Soc Nephrol. 2017;28(5):1631–41. https://doi.org/10.1681/ASN.2016090964 . De Souza Sodre LS, Huaira RMNH, Bastos MG, Colugnati FAB, Coutinho MP, Da Silva Fernandes NM. Screening for fabry disease in kidney disease: A cross-sectional study in males and females. Kidney Blood Press Res. 2017;42(6):1258–65. https://doi.org/10.1159/000485929 . Guo W, Xie Y, Ji P, Li S, Cai G, Chen X. The evolution of the initial manifestations and renal involvement of chinese patients with classical and late-onset Fabry disease at different sexes and ages. BMC Nephrol. 2023;24(1):90. https://doi.org/10.1186/s12882-023-03138-w . Colon C, Ortolano S, Melcon-Crespo C, Alvarez JV, Lopez-Suarez OE, Couce ML, et al. Newborn screening for Fabry disease in the north-west of Spain. Eur J Pediatr. 2017;176(8):1075–81. https://doi.org/10.1007/s00431-017-2950-8 . Mallett A, Kearey PJ, Cameron A, Healy HG, Denaro C, Thomas M, et al. The prevalence of Fabry disease in a statewide chronic kidney disease cohort – Outcomes of the aCQuiRE (Ckd.Qld fabRy Epidemiology) study. BMC Nephrol. 2022;23:169. https://doi.org/10.1186/s12882-022-02805-8 . Sens F, Guittard L, Knebelmann B, Moranne O, Choukroun G, de Précigout V, et al. Prevalence of Fabry disease in patients on dialysis in France. Int J Mol Sci. 2024;25(18):10104. https://doi.org/10.3390/ijms251810104 . Faro DC, Losi V, Rodolico MS, Torrisi EM, Colomba P, Duro G, et al. Sex differences in Anderson–Fabry cardiomyopathy: Clinical, genetic, and imaging analysis in women. Genes (Basel). 2023;14(9):1804. https://doi.org/10.3390/genes14091804 . Mursă A, Militaru S, Rusu E, Onciul S, Neculae G, Adam R, et al. Fabry disease phenotyping in women from the complete Romanian cohort - time for early diagnostic awareness. Rom J Intern Med. 2024;62(4):414–29. https://doi.org/10.2478/rjim-2024-0027 . Di Risi T, Vinciguerra R, Cuomo M, Della Monica R, Riccio E, Cocozza S, et al. DNA methylation impact on Fabry disease. Clin Epigenet. 2021;13:24. https://doi.org/10.1186/s13148-021-01019-3 . Sakuraba H, Tsukimura T, Togawa T, Tanaka T, Ohtsuka T, Sato A, et al. Fabry disease in a Japanese population-molecular and biochemical characteristics. Mol Genet Metab Rep. 2018;17:73–9. https://doi.org/10.1016/j.ymgmr.2018.10.004 . De Alencar DO, Netto C, Ashton-Prolla P, Giugliani R, Ribeiro-dos-Santos Â, Pereira F, et al. Fabry disease: Evidence for a regional founder effect of the GLA gene mutation 30delG in Brazilian patients. Mol Genet Metab Rep. 2014;1:414–21. https://doi.org/10.1016/j.ymgmr.2014.09.002 . Church Smith CL, Roy A, Steeds S, Tuzcuoglu N, Wingrove C, Aitchison K, et al. Underdiagnosis of Fabry disease in minority ethnic groups. Mol Genet Metab Rep. 2025;42:101194. 10.1016/j.ymgmr.2025.101194 . Giugliani R, Politei J, Martins A, Murillo N, Rozenfeld P, Lopera M, et al. Expert review in diagnostic, therapeutic and follow-up of Fabry disease in Latin America based on patient care standards. Mol Genet Metab Rep. 2025;43:101218. https://doi.org/10.1016/j.ymgmr.2025.101218 . Arends M, Biegstraaten M, Wanner C, Sirrs S, Mehta A, Elliott PM, et al. Agalsidase alfa versus agalsidase beta for the treatment of Fabry disease: an international cohort study. J Med Genet. 2018;55(5):351–8. https://jmg.bmj.com/content/55/5/351 . El Dib R, Gomaa H, Carvalho RP, Camargo SE, Bazan R, Barretti P, et al. Enzyme replacement therapy for Anderson-Fabry disease. Cochrane Database Syst Rev. 2016;7CD006663. https://doi.org/10.1002/14651858.CD006663 . Spada M, Baron R, Elliott PM, Falissard B, Hilz MJ, Monserrat L, et al. The effect of enzyme replacement therapy on clinical outcomes in paediatric patients with Fabry disease – A systematic literature review by a European panel of experts. Mol Genet Metab. 2019;126(3):212–23. https://doi.org/10.1016/j.ymgme.2018.04.007 . van der Veen SJ, Körver S, Hirsch A, Hollak CEM, Wijburg FA, Brands MM, et al. Early start of enzyme replacement therapy in pediatric male patients with classical Fabry disease is associated with attenuated disease progression. Mol Genet Metab. 2022;135(2):163–9. https://doi.org/10.1016/j.ymgme.2021.12.004 . İnan R, Meşe M, Bicik Z. Multidisciplinary approach to Fabry disease: from the eye of a neurologist. Acta Neurol Belg. 2020;120:1333–9. https://doi.org/10.1007/s13760-019-01138-y . Hill NR, Fatoba ST, Oke JL, Hirst JA, O'Callaghan CA, Lasserson DS, Hobbs FD. Global prevalence of chronic kidney disease - A systematic review and meta-analysis. PLoS ONE. 2016;11(7):e0158765. https://doi.org/10.1371/journal.pone.0158765 . Schiffmann R, Hughes DA, Linthorst GE, Ortiz A, Svarstad E, Warnock DG et al. Screening, diagnosis, and management of patients with Fabry disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2017;91(2):284–93. https://doi.org/10.1016/j.kint.2016.10.004 Silva CAB, Moura-Neto JA, dos Reis MA, Vieira Neto OM, Barreto FC. Renal manifestations of Fabry disease: A narrative review. Can J Kidney Health Dis. 2021;8. https://doi.org/10.1177/2054358120985627 . Baig S, Edward NC, Kotecha D, Liu B, Nordin S, Kozor R, et al. Ventricular arrhythmia and sudden cardiac death in Fabry disease: a systematic review of risk factors in clinical practice. Europace. 2018;20(FI2):f153–61. https://doi.org/10.1093/europace/eux261 . Hagège A, Réant P, Habib G, Damy T, Barone-Rochette G, Soulat G, et al. Fabry disease in cardiology practice: Literature review and expert point of view. Arch Cardiovasc Dis. 2019;112(4):278–87. https://doi.org/10.1016/j.acvd.2019.01.002 . Dinu IR, Firu ŞG. Fabry disease – current data and therapeutic approaches. Rom J Morphol Embryol. 2021;62(1):5–11. https://doi.org/10.47162/RJME.62.1.01 . Lee HJ, Hsu TR, Hung SC, Yu WC, Chu TH, Yang CF, et al. A comparison of central nervous system involvement in patients with classical Fabry disease or the later-onset subtype with the IVS4 + 919G > A mutation. BMC Neurol. 2017;17:25. https://doi.org/10.1186/s12883-017-0810-9 . 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7330460","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":503713068,"identity":"2b0f08d4-d810-4588-8bba-e96e9880a339","order_by":0,"name":"Sergio Royo Martínez","email":"","orcid":"","institution":"Hospital San Pablo de Coquimbo","correspondingAuthor":false,"prefix":"","firstName":"Sergio","middleName":"Royo","lastName":"Martínez","suffix":""},{"id":503713069,"identity":"b9d03ba3-1b7f-4e4a-9063-289d5f9f6901","order_by":1,"name":"Mauricio Castillo-Montes","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAmklEQVRIiWNgGAWjYDADfghlQaz6BAYGyQYwS4IELQYHiNWi23468XHhDxt74xvJzx4w1BChxexM7mbjGQlpidtupJkbMBwjRssN3m3SPAmHE8xu5LBJMDYQr+W/vfEMErUcYNwgQbQWkF940pITZ5x5ZiaRQJRfjp/d+JjHxs6evz35mcSHGhvCWlBBAqkaRsEoGAWjYBRgBwD7LjI0zivvDwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0001-5034-6622","institution":"Universidad Catolica del Norte Sede Coquimbo","correspondingAuthor":true,"prefix":"","firstName":"Mauricio","middleName":"","lastName":"Castillo-Montes","suffix":""},{"id":503713070,"identity":"8af44368-1370-4f95-8ccb-77bddbe6d396","order_by":2,"name":"Fernando Molt","email":"","orcid":"","institution":"Universidad Católica del Norte Facultad de Medicina: Universidad Catolica del Norte Facultad de Medicina","correspondingAuthor":false,"prefix":"","firstName":"Fernando","middleName":"","lastName":"Molt","suffix":""},{"id":503713071,"identity":"b45d539e-a239-425c-ae32-40391d086471","order_by":3,"name":"Basthian Cortes","email":"","orcid":"","institution":"Hospital San Pablo de Coquimbo","correspondingAuthor":false,"prefix":"","firstName":"Basthian","middleName":"","lastName":"Cortes","suffix":""},{"id":503713072,"identity":"106ba478-f99c-4939-9eea-4652d624c14d","order_by":4,"name":"Muriel Ramírez-Santana","email":"","orcid":"","institution":"Universidad Católica del Norte Facultad de Medicina: Universidad Catolica del Norte Facultad de Medicina","correspondingAuthor":false,"prefix":"","firstName":"Muriel","middleName":"","lastName":"Ramírez-Santana","suffix":""}],"badges":[],"createdAt":"2025-08-08 23:19:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7330460/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7330460/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":90314519,"identity":"7b167966-95cd-4428-b62d-e78c42c173ef","added_by":"auto","created_at":"2025-09-01 10:09:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":697746,"visible":true,"origin":"","legend":"\u003cp\u003eMap of Chile and its bordering countries, highlighting the Coquimbo region and its three provinces.\u003c/p\u003e","description":"","filename":"Figure1MapofCoquimboChile.png","url":"https://assets-eu.researchsquare.com/files/rs-7330460/v1/92741e367b181bdd360fa7c4.png"},{"id":92511259,"identity":"765c55c4-fc24-4118-b840-5639921297d4","added_by":"auto","created_at":"2025-09-30 13:28:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1728557,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7330460/v1/1da3ee54-38f3-490b-b390-da9efb0a44e8.pdf"}],"financialInterests":"","formattedTitle":"Study of prevalence and clinical characterization of Fabry disease in a central northern region of Chile (2013–2023)","fulltext":[{"header":"Introduction","content":"\u003cp\u003eFabry disease (FD), also known as Anderson-Fabry disease, is a lysosomal disease caused by a genetic disorder linked to the X chromosome, produced by mutations in the GLA gene. These mutations cause a deficiency or absence of the lysosomal enzyme alpha-galactosidase A, leading to the progressive accumulation of globotriaosylceramide (Gb3 or GL-3) and other glycosphingolipids in the lysosomes. It is a rare or uncommon, systemic disease whose pathological process begins at an early stage, even during fetal development. However, most patients remain asymptomatic during the first years of life. The clinical manifestations of FD are broad and heterogeneous, and many of them can present as common symptoms.\u003c/p\u003e\u003cp\u003eAmong the most common symptoms are skin lesions, particularly angiokeratomas, which are present in many cases. Cardiac involvement is observed in approximately 40 to 60% of patients, with cardiac muscle hypertrophy being one characteristic manifestation. Kidney disease is also common, with microalbuminuria, proteinuria and progressive deterioration of kidney function. From a neurological point of view, acroparesthesia as a manifestation of small fiber neuropathy are frequent. Ophthalmologically, whorled cornea, vascular tortuosity, and cataracts may be observed. In addition, neuro-otological manifestations have been described, such as progressive or sudden hearing loss. There is, as well, the involvement of the brainstem, central nervous system, or peripheral nervous system. Gastrointestinal disorders affect between 50 and 60% of patients, and bone and pulmonary complications may also occur [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFD occurs in two main forms: the classic form and the non-classic form. The classic form, which has an early onset, is usually more severe and is caused by a complete or almost complete deficiency of the enzyme alpha-galactosidase A (activity\u0026thinsp;\u0026lt;\u0026thinsp;3%). It generally begins in childhood or adolescence and predominantly affects men, although it can also manifest in female carriers. On the other hand, the non-classical form (or late variant) has a later onset, usually presents a milder phenotype, and has variable clinical progression. In these cases, residual enzyme activity is higher (usually\u0026thinsp;\u0026lt;\u0026thinsp;30% in men). Patients may predominantly develop cardiac manifestations (such as cardiomyopathy), renal failure, or cerebrovascular accidents [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe diagnosis of FD is based on the evaluation of clinical signs and symptoms, which can be nonspecific and shared with other pathologies, making it difficult to confirm based on clinical criteria alone. For this reason, biochemical diagnosis is used, which includes measuring the enzymatic activity of alpha-galactosidase A in plasma or leukocytes, and genetic analysis to identify mutations in the GLA gene. In addition, the quantification of globotriaosylceramide (Gb3) in plasma and urine is used as a biomarker of lipid accumulation, useful both for diagnostic confirmation and for monitoring response to treatment [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSpecific treatment of FD is based primarily on permanent enzyme replacement therapy (ERT) using agalsidase alfa or beta. Clinical evidence has shown that the best results (including prevention of irreversible damage) are obtained when ERT is started early and in a timely manner. In addition, therapy with pharmacological chaperones, specifically oral migalastat, has been shown to be an effective and safe alternative in patients who meet the established therapeutic criteria. On the other hand, many patients require supportive treatments or adjuvant therapies, which must be individualized according to clinical symptoms and the degree of involvement of the different organs and systems affected [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eVarious studies worldwide have reported variations in prevalence, which depend on factors such as the methodology used, the population analyzed, and the type of diagnosis used. For example, in 2019, the prevalence was estimated to be 1 in 117,000 live births in Australia [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, more recent research incorporating neonatal screening, genetic sequencing techniques, and the use of biomarkers\u0026mdash;in addition to measuring enzyme activity\u0026mdash;has revealed higher prevalences. In this regard, analysis of databases of pathogenic variants of the GLA gene in men and women has shown a population frequency of 1 in 3,225 people in the population studied, with a higher prevalence in women [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. These findings suggest an upward trend in the prevalence of FD and reinforce the hypothesis that the disease continues to be underdiagnosed.\u003c/p\u003e\u003cp\u003eKnowing the prevalence and distribution of FD is essential to promote early detection, optimize clinical care, and properly guide public health policies. In this context, the Chilean Ministry of Health has established, since 2016, a protocol that provides specific guidelines for the entire network of healthcare providers who treat patients with FD. This document standardizes the diagnostic procedure, inclusion criteria, clinical management, and administration of ERT [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn Chile, the characterization and prevalence of FD are still not precisely known. The only available figures come from the National Health Fund (FONASA) database, which records 139 beneficiaries with financial coverage for FD [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. It is noteworthy that almost half of these patients are concentrated in the north-central part of the country, especially in the Coquimbo Region, where they are treated by a specialized multidisciplinary team at the San Pablo de Coquimbo Hospital. For this reason, the present study aims to establish the prevalence and characterization of Fabry disease in the Coquimbo Region of Chile during the period 2013 to 2023.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eA descriptive cross-sectional study was conducted to determine the prevalence and characterization of FD in the Coquimbo Region between 2013 and 2023. The sample included 69 patients with a confirmed diagnosis of FD, who received treatment and clinical follow-up at the San Pablo Hospital in Coquimbo, the regional referral center for this pathology, in accordance with the guidelines established by the Chilean Ministry of Health [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Of the 69 patients diagnosed, 6 died during the study period.\u003c/p\u003e\u003cp\u003e\u003cb\u003eContext: Geographical, sociodemographic, and health system description of the Coquimbo Region.\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe Coquimbo Region is in north-central Chile, between 29\u0026deg;02\u0026prime; and 32\u0026deg;16\u0026prime; south latitude and from 69\u0026deg;49\u0026prime; west longitude to the Pacific Ocean (Fig.\u0026nbsp;1, left side). Its capital is the city of La Serena, and it is subdivided into three provinces: Elqui (6 municipalities), Limar\u0026iacute; (5 municipalities), and Choapa (4 municipalities) (Fig.\u0026nbsp;1). According to data from the 2024 Census [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], the regional population is 832,864, distributed mainly in the province of Elqui (562,457), followed by Limar\u0026iacute; (178,057) and Choapa (92,350). Eighty-one-point two percent of the population resides in urban areas, while 18.8% live in rural areas [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In terms of social indicators, 7.9% of the regional population lived in poverty in 2022, a figure higher than the national average (6.5%). The employment rate was 64% for men and 40.9% for women [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eChile's healthcare system is mixed, consisting of a public insurer (FONASA), which covers approximately 77% of the national population [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], and private insurers grouped together in the Health Insurance Institutions (ISAPRE), in addition to the Armed Forces' healthcare system. In 2015, Law No. 20,850 was enacted, establishing a financial protection system for high-cost diagnoses and treatments, applicable to beneficiaries of all social security schemes and financed by FONASA [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The health conditions covered by this law include FD. The Coquimbo Region has a public healthcare network organized into different levels of complexity. It has three high-complexity hospitals located in the most populated municipalities: Coquimbo, La Serena, and Ovalle; a medium-complexity hospital in the municipality of Illapel; and five low-complexity or community facilities in Andacollo, Combarbal\u0026aacute;, Los Vilos, Salamanca, and Vicu\u0026ntilde;a. In addition, the public primary healthcare system in the region consists of 358 facilities offering different levels of care and 26 emergency services distributed throughout the region [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eHealth care of patients with FD: Suspicion, diagnosis, treatment, and follow-up\u003c/h2\u003e\u003cp\u003eIn the Coquimbo Region, the diagnosis and treatment of FD is centralized exclusively at the San Pablo Hospital in Coquimbo, the only facility in the region that has a neurology department and the Multidisciplinary Team for the Study and Treatment of Fabry Disease (EMETEF).\u003c/p\u003e\u003cp\u003ePatients with suspected or confirmed FD can access the Ministry of Health public financial protection system for high-cost diagnoses and treatments, regardless of whether they are affiliated with the public (FONASA) or private health system, whose access is subject to evaluation and confirmation by an accredited committee of experts. There are two main ways to enter this system. The first is the diagnostic suspicion modality, aimed at patients with a well-founded suspicion of FD, usually formulated by medical specialists such as neurologists, internists, geneticists, or pediatricians. In men, the diagnosis is confirmed by measuring the enzymatic activity of alpha-galactosidase A in leukocytes, supplemented by molecular genetic analysis. In women, due to phenotypic variability and the possibility of normal enzyme activity, molecular genetic testing is required for diagnostic confirmation. The second is the therapeutic modality, which is aimed at patients with a previously confirmed diagnosis who require second-line treatment or treatment with greater therapeutic complexity. Standard treatment consists of ERT with agalsidase alfa or agalsidase beta, which must be administered by authorized providers and is covered by Law No. 20,850 [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eParticipants, instruments, ethical aspects, data collection and analysis\u003c/h3\u003e\n\u003cp\u003eThe study included all 69 people diagnosed with FD in the Coquimbo Region between 2013 and 2023 who received treatment at the San Pablo Hospital in Coquimbo. For data collection, a questionnaire was designed using the Google Forms platform (Google LLC, Mountain View, CA, USA), without including fields that would allow the personal identification of patients, to guarantee confidentiality. The instrument was designed to be completed by the treating physician or a member of EMETEF and included instructions for its application and data recording. The study protocol was approved by the Scientific Ethics Committee of the Faculty of Medicine of the Catholic University of the North, under Resolution No. 56/2023. Institutional authorization was also obtained from the San Pablo Hospital in Coquimbo, the healthcare center where all patients with FD in the region are treated and whose clinical records are kept. The questionnaire was answered using information contained in clinical records and hospital files. The variables collected included: sex, age, municipality of residence, type of health insurance, year of initiation of therapy, type of enzyme replacement therapy, use of chronic medications, type of clinical manifestation, and type of genetic mutation. The analysis of clinical manifestations focused on the main organs or systems affected: peripheral nervous system (PNS), renal system (RF), heart (HT), and central nervous system (CNS). Patients were classified according to the type of mutation, specifically identifying the presence or absence of the classic mutation of the disease.\u003c/p\u003e\u003cp\u003eThe prevalence of FD was estimated considering the 69 confirmed cases throughout the study period, without excluding deceased patients. The denominator used was the average regional population projection for the years 2013 to 2023, according to the National Institute of Statistics (INE) data [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], and the 95% confidence interval was calculated.\u003c/p\u003e\u003cp\u003eFor statistical analysis, contingency tables and the chi-square test (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) were used to evaluate associations between sex and type of condition, as well as between sex and chronic medication use. The comparison between independent groups\u0026mdash;such as age, presence of specific clinical manifestations, and use of chronic medications\u0026mdash;was performed using the Student's t-test, the nonparametric Mann-Whitney U test, or Welch's t-test in cases where the assumption of homogeneity of variances was not met (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In addition, a nonparametric correlation (Spearman's Rho) was performed between the number of affected systems and the number of chronic medications consumed with age. Data processing and analysis were performed using JASP software version 0.18.3.0 and IBM SPSS Statistics version 26.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eNinety-four percent (94%) of the patients included in the study had the classic form of FD, and 92.8% carried the P259R mutation. The demographic and clinical characteristics of the 69 patients are detailed in Table 1. Fifty-eight percent were women, with a female-to-male ratio of 1.4:1. The age of the participants ranged from 6 to 73 years, with a mean of 35.8 \u0026plusmn; 18.67 years; when broken down by sex, the mean age was 38.5 \u0026plusmn; 19.75 years in women and 32.0 \u0026plusmn; 16.34 years in men. 86.2 percent of patients were over 14 years of age. In terms of geographical distribution, the majority resided in the province of Elqui (92.8%), specifically in the municipality of Coquimbo (81.2%). See Figure 1, right side. Concerning the type of health insurance, 97% were affiliated with the public system and only 3% had private insurance.\u003c/p\u003e\n\u003cp\u003eRegarding ERT, 58.0% of patients began treatment in 2016, coinciding with the entry into force of Law No. 20,850. However, by 2023, 10.1% had not yet begun ERT. Agalsidase alfa was used in 55.1% of cases, and among patients who received ERT, 61.3% were treated with agalsidase alfa and 38.7% with agalsidase beta.\u003c/p\u003e\n\u003cp\u003eAbout the clinical manifestations and multisystem involvement characteristic of FD, 71.0% of patients had PNS involvement, followed by RF involvement in 39.1%. No statistically significant differences were observed between sex and type of involvement.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn addition to enzyme treatment, 46.4% of patients used complementary medications due to the type of involvement and the presence of chronic comorbidities, and in this group, women accounted for 69.5%. The most used drugs were analgesics (47.8%), antihypertensives (42.0%), and anti-neuropathic (27.5%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 1. Characterization of patients with Fabry disease, Coquimbo Region, Chile, 2013\u0026ndash;2023.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"489\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 150px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eMen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e42.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eWomen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e58.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge range of therapy initiation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e0 to 14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e17.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e15 to 29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e24.6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e30 to 44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e27.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e45 to 59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e15.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e60 to 74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e14.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e75 and over\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDeath rate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e7.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of mutation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eP259R\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e95.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 180px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eRPCF4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e2.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003epW81X\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e1.4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eProvince\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eElqui\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e92.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eLimar\u0026iacute;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e7.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eChoapa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of insurance\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003ePublic (FONASA)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e97.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003ePrivate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e2.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEnzyme replacement therapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eAgalsidasa alfa\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e55.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eAgalsidasa beta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e34.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eWithout ERT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e10.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"4\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of clinic involvement\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003ePeripheral Nervous System (PNS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e71.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eRenal System (RF)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e39.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eHeart (HT)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e37.7%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eCentral Nervous System (CNS)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e14.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"8\" style=\"width: 180px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of medication for chronic use\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eAnalgesics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e47.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eAntihypertensives\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e42.0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eAntineuropathics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e27.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eHypolipidemic agents\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e23.2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eAntiplatelet agents\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e20.3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eAntiarrhythmics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e10.1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eAnticoagulants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e5.8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eAntivertiginants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e2.9%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSource: own elaboration\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe prevalence rates of FD in the Coquimbo Region are presented in Table 2. The overall prevalence was 8.44 per 100,000 inhabitants (95% CI: 6.44\u0026ndash;10.43), with a higher rate observed in women compared to men. Among the three provinces in the region, Elqui had the highest prevalence, particularly in the commune of Coquimbo, with a rate of 22.45 per 100,000 inhabitants (95% CI: 16.57\u0026ndash;28.33), the highest in the entire territory analyzed. In terms of distribution by age group, the highest prevalence rates were observed in the 30\u0026ndash;44 and 60\u0026ndash;74 age ranges, with similar values between the two.\u003c/p\u003e\n\u003cp\u003eTable 2: Prevalence of Fabry disease in the Coquimbo Region, Chile, 2013\u0026ndash;2023.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"614\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCategory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePopulation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of cases\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRate per 100000 inhabitants\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eC.I. 95%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLower\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUpper\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eMen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e400573\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e7.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e4.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e9.87\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eWomen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e416895\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e9.59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e6.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e12.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"6\" style=\"width: 121px;\"\u003e\n \u003cp\u003eAge range of therapy initiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e0 to 14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e169436\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e7.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e3.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e11.08\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e15 to 29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e179244\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e9.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e4.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e13.99\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e30 to 44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e173370\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e10.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e6.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e15.88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e45 to 59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e152399\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e7.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e2.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e11.48\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e60 to 74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e99182\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e10.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e3.83\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e16.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e75 and over\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e43837\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eElqui Province\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e542112\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e64\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e11.8\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e8.91\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e14.69\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eCommune\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eCoquimbo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e249437\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e22.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e16.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e28.33\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eLa Serena\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e242699\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e1.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e3.26\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eVicu\u0026ntilde;a\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e29261\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e3.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003en.c.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003en.c.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eAndacollo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e11698\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e8.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003en.c.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003en.c.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003ePaihuano\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e4631\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e43.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003en.c.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003en.c.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eLa Higuera\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e4386\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLimar\u0026iacute; Province\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e181813\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2.75\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.33\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5.16\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eCommune\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eOvalle\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e119409\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e3.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e6.63\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eMonte Patria\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e32266\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eCombarbal\u0026aacute;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e13807\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003ePunitaqui\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e11961\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e8.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003en.c.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003en.c.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003eR\u0026iacute;o Hurtado\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e4370\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eChoapa Province\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 89px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e93543\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 210px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal Coquimbo Region\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e817468\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e69\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e8.44\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6.44\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 80px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e10.43\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003en.c. not calculable. Source: own elaboration\u003c/p\u003e\n\u003cp\u003eTable 3 presents a comparison of ages at ERT initiation according to the presence or absence of clinical manifestations and medicines for chronic use. It was observed that patients with FD who presented some type of clinical condition had a significantly higher average age of therapy initiation than those without clinical manifestations. When analyzing the different types of conditions, it was found that patients with PNS involvement were significantly younger than the other groups, with an average age of 39.2 \u0026plusmn; 17.6 years (p = 0.015). Likewise, chronic consumption of medications for the relief of other types of symptoms also showed differences in terms of age, except for anti-neuropathic and antivertiginous drugs. In general, those consuming this type of medication were older at the time of starting treatment.\u003c/p\u003e\n\u003cp\u003eTable 3: Clinical involvement according to age at the start of ERT in patients with FD, Coquimbo Region, Chile, 2013-2023.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"607\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAffected System\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"bottom\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eWith affectation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" valign=\"bottom\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo affectation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDifference in age (mean) according to affected system\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge of therapy initiation (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge of therapy initiation (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eS.D.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eS.D.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePNS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e39.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e17.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e27.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e19.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eRF\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e49.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e15.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e26.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e14.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e52.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e52.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e25.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e13.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026lt;0,001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCNS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e52.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e32.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e18.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"3\" style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eType of Medication\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConsumption\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo consumption\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 125px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDifference in age (mean or median) by use of medications\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge of therapy initiation (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge of therapy initiation (years)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eS.D.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eS.D.\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMedian\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003e\u003csup\u003e1\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003ep\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnalgesics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e41.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e18.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e30.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e17.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntihypertensives\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e51.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e12.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e24.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e13.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntineuropathics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e39.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e34.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e18.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e0.324\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypolipidemic agents\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e58.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e15.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnti-aggregants\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e58.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e10.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e59\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e15.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntiarrhythmics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e61.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e7.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e32.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e17.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnticoagulants\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e66.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e6.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e33.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e17.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 136px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAntivertiginous\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e35.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e18.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e0.191\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eERT: Enzyme Replacement Therapy; PNS: Peripheral Nervous System; RF: Renal System; HT: Heart; CNS: Central Nervous System; \u003csup\u003e1\u003c/sup\u003eStudent\u0026acute;s Test; \u003csup\u003e2\u003c/sup\u003eWelch\u0026apos;s t-test; \u003csup\u003e3\u003c/sup\u003eMann-Whitney U test. Source: own elaboration.\u003c/p\u003e\n\u003cp\u003eTable 4 shows the correlation indices between the number of systems affected and the number of chronic medications with the age of treatment onset. It can be observed that age has a significant influence on both the number of systems affected and the number of chronic medications consumed by patients.\u003c/p\u003e\n\u003cp\u003eTable 4: Correlation between affected systems and chronic medications at the beginning of treatment, Coquimbo Region, Chile, 2013-2023.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"529\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 307px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 138px;\"\u003e\n \u003cp\u003eSpearman\u0026acute;s Rho\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 307px;\"\u003e\n \u003cp\u003eNumber of systems affected - age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 307px;\"\u003e\n \u003cp\u003eNumber of drugs of chronic use - age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 138px;\"\u003e\n \u003cp\u003e0.747\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 85px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSource: own elaboration\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe prevalence observed in this study was 8.44 per 100,000 inhabitants in the Coquimbo Region, an elevated frequency considering that almost half of the cases registered in the country are concentrated in this region. This rate far exceeds those reported in various international studies, where the prevalence of FD varies between 1 per 40,000 and 140,000 inhabitants [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Similarly, prevalences ranging from 0.015 to 0.85 per 100,000 inhabitants have been reported, which may underestimate the true magnitude of the disease, as neonatal screening studies have revealed significantly higher figures [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Along these lines, a prevalence at birth of 1.25 per 100,000 inhabitants has been estimated in Australia and some European countries, although this could also be underestimated due to the variability in the life expectancy of patients with FD [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAlthough EF is classified as a rare or low-frequency pathology, its occurrence in the Coquimbo Region is of special interest, as evidenced by the findings of this study. An outstanding characteristic is the age distribution of the patients: approximately 46% are under 30 years of age, and the average age is slightly lower in men than in women, which agrees with what has been reported in several previous publications [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eRegarding sex, this study found a higher prevalence of FD in women than in men, which contrasts with most internationally published studies. Previous studies, both in populations with chronic kidney disease (CKD) with and without dialysis and in neonatal screening programs, report a higher frequency of FD in males than in females, with high variability, being the prevalences much higher in places where neonatal screening is performed [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. These differences can be explained by the genetic basis of the disease, which is linked to the X chromosome. In men, who have a single X chromosome, clinical manifestations tend to appear earlier, with greater severity and accelerated progression. In women, however, the clinical presentation is more heterogeneous, with frequently subtle symptoms, later onset, greater survival, and variability in severity, attributable to random inactivation of the X chromosome. This can result in both mild and severe phenotypes, depending on the degree of expression of the mutated allele of the GLA gene, which is responsible for encoding the enzyme alpha-galactosidase A. As a result, women tend to have higher enzyme levels and lower concentrations of liso-Gb3 compared to men, which makes early diagnosis difficult [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. In addition, many women are diagnosed as asymptomatic carriers after family screening, which may have contributed to finding a higher proportion of female cases. The finding of a higher prevalence of FD in women in this study population suggests the existence of particular factors in the Coquimbo Region that could influence phenotypic expression, or the diagnostic strategies implemented. This result highlights the need for further regional genetic, epidemiological, and clinical studies to better understand this pattern and its implications for the detection and management of the disease.\u003c/p\u003e\u003cp\u003eThe high prevalence of FD in the province of Elqui accounts for approximately 43% of all cases recorded nationwide, with most patients concentrated in the commune of Coquimbo. It has been documented that the prevalence of FD can vary significantly depending on specific mutations and predominant genetic patterns in different populations and geographical regions [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. In this study, over 90% of patients have the P259R mutation, suggesting the possible existence of a founder effect. Consequently, it is pertinent to investigate the origin and age of this mutation through advanced genotyping studies and identification of shared haplotypes. These analyses would make it possible to determine the degree of consanguinity among the cases reported in the province, as well as to evaluate the possible influence of minority ethnic components that could be modulating the genomic architecture and clinical manifestations of the disease [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Furthermore, many of these patients are enrolled in the public health system, suggesting a less favorable socioeconomic situation. This geographic and socioeconomic distribution reinforces the congenital and rare nature of this metabolic disease and has prompted the implementation of a specialized regional multidisciplinary team for its study, diagnosis, and treatment.\u003c/p\u003e\u003cp\u003e The existence of a specialized and multidisciplinary center for the care of FD at the Hospital San Pablo de Coquimbo is in line with the recommendations of experts in Latin America, who emphasize the need to strengthen the capacities of the health system for the timely diagnosis, comprehensive treatment and continuous follow-up of patients. Likewise, this type of initiative is consistent with policies that promote the financing of medication and comprehensive care for rare diseases [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eConcerning ERT, no differences were observed in the frequency of use between agalsidase alfa and agalsidase beta. This is probably because, once diagnosed with CF and the therapeutic requirement established, patients are randomly assigned to one or the other drug by FONASA. Both treatments have demonstrated comparable efficacy, with no significant differences in clinical manifestations, even when administered at different doses or frequencies. Likewise, there has been no evidence of a differential impact on long-term mortality between the two formulations [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. It should be noted that some patients diagnosed with FD did not receive enzyme replacement therapy, which could be explained by the absence of symptoms at the time of diagnosis, especially in pediatric patients who did not yet meet the criteria established in the protocol [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, clinical guidelines recommend starting ERT early, even before the onset of irreversible organ damage, with the aim of modifying the natural course of the disease, relieving pain, and improving quality of life. Several studies have shown that timely initiation of ERT can normalize plasma globotriaosylceramide (GL-3) levels, improve gastrointestinal symptoms, and reduce the incidence of renal and cardiac complications [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. This is consistent with the findings of the present study, which indicate that the older the age at diagnosis, the greater the number of systems affected in patients.\u003c/p\u003e\u003cp\u003eGiven the multi-organ nature of FD, in addition to ERT, patients may require chronic use of one or more symptomatic medications. In Chile, these drugs can be provided free of charge through FONASA, or they may represent an out-of-pocket expense for the patient. In this study, it was observed that 46.4% of patients received additional pharmacological treatment, with analgesics being the most frequently used. This finding is probably related to the high prevalence of neuropathic pain, one of the characteristic and initial symptoms of FD. The low frequency of use of other chronic medications could be explained by the effectiveness of ERT in reducing or attenuating the signs and symptoms associated with the disease [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Likewise, greater use of complementary medications was observed as the age of the patients increased.\u003c/p\u003e\u003cp\u003eIn the analysis of the different types of systemic involvement in patients with FD, it was observed that those with PNS involvement had a significantly lower average age (39.2 years) compared to patients with RF, HT, and CNS involvement, whose average ages were higher. Similarly, people who used antineuropathic drugs also belonged to the younger age group, with no significant differences in age compared to those who did not receive such medication, and the effect size was small. This finding is consistent with the literature, which indicates that one of the first clinical manifestations of FD\u0026mdash;often from childhood or adolescence\u0026mdash;is acroparesthesia and Fabry neuropathic crises, characterized by acute neuropathic pain with a burning, stinging, or tingling sensation that can radiate to the distal extremities or other body regions [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. In relation to CKD, its association with advanced age is widely recognized [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e], which was corroborated in this study population. It has been reported that patients with FD may begin to show clinically relevant renal impairment \u0026mdash;including cases requiring dialysis replacement therapy\u0026mdash; from the age of 30, with progression intensifying between the ages of 40 and 50 [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. This pattern reinforces the relationship observed between older age and renal involvement in the patients studied. Similarly, heart manifestations (HT), such as left ventricular hypertrophy or hypertrophic cardiomyopathy, tend to occur at more advanced stages, generally after age 30, and are associated with higher cardiac morbidity and mortality [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e, \u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. On the other hand, CNS involvement has also been linked to older ages, with symptoms ranging from headaches and dizziness to severe manifestations such as neuro-otological disorders or cerebrovascular events [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe main strength of the study is the minimal probability of patient loss, since all patients, both from public and private centers, are registered in the program and were included in the study. All diagnoses were validated, and data was even available for six deaths during the period. The only source of possible losses may be people who have moved out of the region or who are awaiting evaluation by a specialist. A second limitation of the study is that, with the method used, it is not possible to calculate confidence intervals for prevalence rates in municipalities with small populations, where 1 or 2 cases result in high rates with confidence intervals ranging from negative values. Finally, there is a limitation in the recording of patient age, since it is not the age of symptom onset, but rather the age at which each patient enters the program and begins enzyme replacement therapy.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe prevalence of FD in north-central Chile is the highest recorded nationally and internationally, with a significant concentration of cases in the municipality of Coquimbo, suggesting consanguinity. Unlike what has been reported in the international literature, in this region the disease predominantly affects women. The age of treatment initiation significantly influences both the number of systems affected and the number of chronic medications consumed by patients, emphasizing the need for early diagnosis through screening and recommending genetic counseling for already identified patients.\u003c/p\u003e\u003cp\u003eThe findings open the possibility of conducting more in-depth research on the genomic representation of this population, with the aim of identifying possible common origins and ethnic components that may influence the clinical expression and symptoms of FD. The region has a strategic advantage for this type of study, as it has a specialized, multidisciplinary center for FD at the San Pablo Hospital in Coquimbo, which serves as a regional reference for the diagnosis, treatment, and follow-up of this disease.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eCKD: Chronic kidney disease\u003c/p\u003e\n\u003cp\u003eCNS: Central nervous system\u003c/p\u003e\n\u003cp\u003eEMETEF: Multidisciplinary Team for the Study and Treatment of Fabry Disease\u003c/p\u003e\n\u003cp\u003eERT: Enzyme replacement therapy\u003c/p\u003e\n\u003cp\u003eFD: Fabry disease\u003c/p\u003e\n\u003cp\u003eFONASA: National Health Fund\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eGb3: Globotriaosylceramide\u003c/p\u003e\n\u003cp\u003eHT: Heart\u003c/p\u003e\n\u003cp\u003eINE: National Institute of Statistics\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eISAPRE: Private Health Insurance Institutions\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePNS: Peripheral nervous system\u003c/p\u003e\n\u003cp\u003eRF: Renal system\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Scientific Ethics Committee of the Faculty of Medicine of the Universidad Católica del Norte (Res. CECFAMED-UCN REV N°56/2023).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study database may be made available upon request to the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors did not receive funding from any organization for the presented research. The study was the thesis of the main author, to obtain the degree of Master in Public Health.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSR, FM and MC-M conceptualized and designed the study, FM, BC and SR collected the data, SR and MC-M did the methodology, MC-M and MR-S analyzed and interpreted the data, MC-M and SR drafted and wrote the final manuscript, MR-S and MC-M reviewed and edited the manuscript. All authors read and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo Juan Correa Parra, geographer, for designing the map (Figure 1). To the Multidisciplinary Team for the Study and Treatment of Fabry Disease of Coquimbo Hospital.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGermain DP. Fabry disease. 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Arch Cardiovasc Dis. 2019;112(4):278\u0026ndash;87. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.acvd.2019.01.002\u003c/span\u003e\u003cspan address=\"10.1016/j.acvd.2019.01.002\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDinu IR, Firu ŞG. Fabry disease \u0026ndash; current data and therapeutic approaches. Rom J Morphol Embryol. 2021;62(1):5\u0026ndash;11. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.47162/RJME.62.1.01\u003c/span\u003e\u003cspan address=\"10.47162/RJME.62.1.01\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee HJ, Hsu TR, Hung SC, Yu WC, Chu TH, Yang CF, et al. A comparison of central nervous system involvement in patients with classical Fabry disease or the later-onset subtype with the IVS4\u0026thinsp;+\u0026thinsp;919G\u0026thinsp;\u0026gt;\u0026thinsp;A mutation. BMC Neurol. 2017;17:25. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12883-017-0810-9\u003c/span\u003e\u003cspan address=\"10.1186/s12883-017-0810-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Fabry Disease, genetic diseases, inborn, prevalence, cross-sectional studies","lastPublishedDoi":"10.21203/rs.3.rs-7330460/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7330460/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eFabry disease (FD) is an X-linked genetic disorder, resulting in deficiency or absence of the enzyme alpha-galactosidase A, causing progressive multisystem involvement. Diagnosis combines clinical evaluation, biochemical testing and genetic analysis. Early initiation of enzyme replacement therapy (ERT) is crucial to prevent irreversible damage. In Chile, information on prevalence and clinical characteristics of FD is limited. The study aimed to estimate the prevalence of FD and characterize patients in the Coquimbo Region of Chile, between 2013 and 2023.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eDescriptive cross-sectional study of 69 patients with FD. The following variables were recorded in an anonymized clinical questionnaire: sex, age, residence, health insurance, start of therapy, type of ERT, chronic medication, type of clinical manifestation and type of genetic mutation. Descriptive statistics and correlation tests were used for the analysis. Prevalence was calculated on the regional population average projected by the National Institute of Statistics (INE) for the period 2013\u0026ndash;2023.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe regional prevalence rate was 8.44 per 100,000 inhabitants (95% CI: 6.44\u0026ndash;10.43), with a particularly high value in the commune of Coquimbo (22.45 per 100,000 inhabitants). The majority were women (58.0%), with a mean age of 35.8 years. Ninety-four percent had the classical form of FS, and 95.7% carried the P259R mutation. ERT was initiated in 2016 for 58% of patients, and 55.1% received agalsidase alfa. Peripheral nervous system (PNS) involvement was present in 71.0% and renal involvement in 39.1%. 46.4% used complementary drugs, mostly analgesics, antihypertensives and antineuropathics, whose consumption increases with age. The older the patient, the greater the number of affected systems. Those with PNS involvement were younger.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe Coquimbo Region has the highest recorded prevalence of FD in Chile, concentrated in the commune of Coquimbo. The age of entry into treatment significantly influences both the number of affected systems and the chronic use of drugs. The high frequency of the P259R mutation suggests the need for genetic studies to explore possible common origins and ethnic factors that influence the clinical expression of the FD. A specialized FD care center is a strength for conducting further research on the disease.\u003c/p\u003e","manuscriptTitle":"Study of prevalence and clinical characterization of Fabry disease in a central northern region of Chile (2013–2023)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-01 10:08:48","doi":"10.21203/rs.3.rs-7330460/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c3402a3f-6554-43f9-b3c0-ea637f4a2eb0","owner":[],"postedDate":"September 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-30T13:20:33+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-01 10:08:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7330460","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7330460","identity":"rs-7330460","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}