Burosumab in infants with X-linked hypophosphatemic rickets: a case series

Burosumab in infants with X-linked hypophosphatemic rickets: a case series | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Burosumab in infants with X-linked hypophosphatemic rickets: a case series Ravit Regev, Avivit Brener, Nitzan Dror, Raphael Krespi, Rebeca Rapalino, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6385587/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Jan, 2026 Read the published version in Orphanet Journal of Rare Diseases → Version 1 posted 5 You are reading this latest preprint version Abstract Background: X-linked hypophosphatemic rickets (XLH) is a rare inherited metabolic bone disorder caused by excess fibroblast growth factor 23 (FGF23), leading to hypophosphatemia and rickets. Burosumab, a human monoclonal antibody targeting FGF23, was approved for the treatment of XLH in April 2018. By 2022, the FDA extended its approval to include children as young as six months of age. Objectives: To describe three infants with XLH who began burosumab therapy before one year of age and were monitored for at least one year. Design: Case series. Methods: Clinical outcomes, including anthropometric measures, skeletal outcomes (Rickets Severity Score [RSS], mechanical axis deviation [MAD], and neck-shaft angle [NSA]), and laboratory parameters, were assessed in a real-world setting. Results: Two patients demonstrated satisfactory linear growth, and one experienced growth faltering, possibly due to sleep-disordered breathing or phosphate imbalance. These patients received higher doses of burosumab than the current guideline recommendations for achieving treatment goals aimed at normalizing phosphate levels. The patient’s phosphate levels improved but did not normalize. Bone pain was not formally assessed, but parents reported improvements in their children’s conditions. Importantly, two patients with assessable mechanical axes demonstrated neutral mechanical axis deviations, indicating improved lower limb alignment and supporting the therapeutic efficacy of burosumab. All three patients had favorable RSS outcomes, and none developed long bone diaphyseal bowing or coxa vara following this early initiation of burosumab treatment. Conclusion: This case series demonstrated potential benefits of early initiation of burosumab treatment for XLH by showing improvements in growth, phosphate levels, and skeletal outcomes. Burosumab appears well tolerated in infancy, but further research is needed to refine dosing strategies and assess its long-term safety and therapeutic efficacy in young patients with XLH. Meticulous monitoring and individualized care are essential throughout treatment. X-linked hypophosphatemic rickets XLH burosumab infants linear growth rickets score phosphate levels skeletal health Figures Figure 1 Plain language summary This case series followed three infants with X-linked hypophosphatemic rickets (XLH) who initiated burosumab treatment at 6 months of age, filling a significant knowledge gap in early intervention. Despite requiring higher-than-recommended dosing, burosumab demonstrated favorable outcomes in terms of growth parameters and skeletal development over a minimum one-year follow-up. Two patients maintained normal growth trajectories, whereas one experienced temporary growth faltering, which resolved after adenoidectomy. Importantly, neutral mechanical axis deviation was achieved, indicating effective prevention of lower limb deformities. No significant adverse effects were observed. Despite limitations such as a small sample size and short follow-up, these findings suggest that early burosumab therapy can improve outcomes in infantile XLH patients. Further research is needed to refine dosing protocols and assess long-term safety and efficacy in this young population. Introduction X-linked hypophosphatemic rickets (XLH) is a rare inherited progressive metabolic bone disorder with an estimated prevalence of 1.3–4.8 cases per 100,000 individuals.( 1 – 3 ) XLH results from a mutation in the phosphate-regulating endopeptidase homolog on the X chromosome ( PHEX ) gene, leading to excess fibroblast growth factor 23 (FGF23). This mutation causes renal phosphate wasting and insufficient production of 1,25-dihydroxyvitamin D (1,25(OH)2D), resulting in reduced intestinal phosphate absorption and, ultimately, hypophosphatemia.( 4 ) Children with XLH exhibit skeletal characteristics of rickets and osteomalacia, including progressive bowing deformities of the lower limbs, disproportionate short stature, bone pain, dental abscesses, and proximal muscle weakness, all of which impair physical function and diminish quality of life. ( 5 ) Since the 1980s, individuals with XLH have been treated with multiple daily doses of oral phosphate and active vitamin D. While this conventional therapy can improve clinical features, it carries risks, such as nephrocalcinosis and hyperparathyroidism, and can be burdensome due to frequent dosing, gastrointestinal side effects, and the need for careful monitoring. ( 4 ) ( 6 ) In April 2018, burosumab, a human monoclonal antibody against FGF23, received FDA approval in the USA and conditional approval in Europe for the treatment of children with XLH aged over one year, as well as adolescents with growing skeletons.( 7 ) In 2020, the Israeli Ministry of Health approved burosumab for children with XLH older than one year of age. A phase three international multicenter trial demonstrated that burosumab is superior to conventional therapy for improving rickets scores, growth, limb deformities, and mobility in children aged 1–12 years.( 6 ) This was supported by real-world evidence that reportedly holds promise for improvements in linear growth, rickets scores, and laboratory metrics in pediatric patients treated with burosumab.( 8 , 9 ) In 2022, the FDA extended its approval to children as young as six months of age.( 7 ) Data on improvements in linear growth and biochemical markers with burosumab treatment initiated before the age of one year, however, are limited. Makite et al. demonstrated that starting conventional treatment before the age of one year leads to better rickets scores in patients with XLH, although it does not completely normalize skeletal development.( 10 ) This case series describes three patients with XLH who began burosumab therapy in infancy and were followed for at least one year, with a focus on its impact on linear growth, the rickets score, and laboratory parameters in real-life settings. Patients and methods Three infants with XLH followed at the Metabolic Bone Clinic at Dana-Dwek Children’s Hospital, Tel Aviv Sourasky Medical Center, and the Endocrine Unit at Meir Medical Center began burosumab treatment before the age of one year. Routine care at our centers included in-clinic visits every three to six months during which anthropometric measurements were performed along with evaluations of metabolic laboratory parameters. Medical interviews were conducted to assess treatment adherence and efficacy and to monitor any adverse effects. Skeletal radiographs were obtained every 6 to 12 months to assess the severity of rickets as part of routine clinical care. Individualized treatment plans were based upon a composite evaluation of these clinical parameters. The three patients were started on conventional therapy with oral phosphate and active vitamin D shortly after diagnosis, in accordance with standard XLH treatment guidelines. ( 11 ) Conventional therapy was discontinued seven days before the initiation of burosumab, which was administered at a dose of 0.8 mg/kg of body weight, rounded to the nearest 10 mg according to the protocol. ( 12 ). The dosage was gradually adjusted on the basis of laboratory results, in accordance with practice guidelines.( 13 ) Clinical characteristics, biochemical markers, findings on skeletal radiographs, and growth parameters were collected and analyzed. Weight was measured with a tabletop electronic infant scale with an attached measuring rod (Model 374 + Measuring Rod 233, SECA, Gmbh & Co., Germany), and crown-heel length was measured with the infant in the supine position. The World Health Organization (WHO) Growth Standards were used for infants 0 to two years of age, and z-scores were tallied. ( 14 ) The weight-to-length ratio was calculated as an indicator of weight status in children younger than two years of age. ( 15 ) Body mass index (BMI) of older children was calculated by dividing body weight in kilograms by height in meters squared, and height, weight, and BMI z-scores were determined using sex- and age-specific CDC 2000 growth charts. ( 16 ) Laboratory blood samples were collected prior to burosumab injections and analyzed for serum levels of phosphorus, calcium, creatinine, alkaline phosphatase (ALP), 25-hydroxy vitamin D, 1,25-dihydroxyvitamin D (1,25 vit D), intact parathyroid hormone (PTH), and intact FGF23. Spot urine tests were performed to measure phosphorus, calcium, and creatinine levels. Total reabsorption of phosphate (TRP) was calculated by mean of an online calculator and is presented as a percentage. ( 17 ) The tubular maximum transport of the phosphate-to-glomerular filtration rate (TmP/GFR) was calculated from values in serum and spot urine as previously described elsewhere. ( 18 ) Skeletal radiographs were obtained as needed for routine clinical care and evaluated by two independent bone health specialists (RR and LZ) who used the Thacher Rickets Severity Score (RSS). The images were scored on a scale from 0 to 6, with higher scores indicating greater severity of rickets. The mechanical axis of the lower limb, also referred to as the Mikulicz line, was determined by drawing a line from the center of the femoral head to the center of the ankle. Under normal conditions, this axis passes approximately 8 mm medial to the midpoint of the knee. Deviations from this range signify alignment abnormalities. Specifically, an axis that shifts laterally indicates valgus alignment, whereas a medial shift suggests varus alignment. The extent of this deviation is termed the mechanical axis deviation (MAD) ( 19 ). The femoral neck angle, a radiological measurement that refers to the angle formed between the axis of the femoral neck and the axis of the femoral shaft ( 19 ), was assessed by a pediatric orthopedist. Socioeconomic position by home address was analyzed using the Israel Central Bureau of Statistics’ Characterization and Classification of Statistical Areas. Neighborhoods or localities were categorized into 10 socioeconomic clusters, with 1 being the most deprived and 10 being the most affluent, which were grouped into low ( 1 – 4 ), medium ( 5 – 7 ), and high ( 8 – 10 ) categories. The socioeconomic index, ranging from − 2.797 to 2.590, is based upon 14 variables reflecting demographics, education, standard of living, and employment.( 20 ) Case series Patient 1. This 5-year 2-month-old female presented to our clinic shortly after birth. She was born preterm at 35 + 5 weeks of gestation, with a birth weight appropriate for gestational age (2.685 kg), as one of a pair of twins. Prenatal genetic testing via amniocentesis identified a PHEX mutation, although it was initially unclear which twin was affected. At 19 days of age, the patient was hospitalized for neonatal fever, during which blood tests revealed hypophosphatemia, establishing the diagnosis of XLH. Conventional treatment with phosphate supplements and calcitriol was initiated at 2 months of age. At 6 months, burosumab therapy was started at a dose of 10 mg (1.38 mg/kg), was administered at home by a nurse practitioner, and was titrated to a maximum of 40 mg (2.22 mg/kg). Despite this high-dose burosumab regimen, serum phosphate levels remained below the lower limit of normal for age and sex. At the age of 5 years, growth remained stable, with height consistently measuring between the 10th and 25th percentiles and weight at the 50th percentile (BMI between the 85th and 90th percentiles). The patient's mother reported significant improvement in bone pain and physical activity, although some residual musculoskeletal discomfort persisted. The skeletal outcomes showed a favorable RSS and neutral MAD without femoral bowing and with only mild tibial bowing (Fig. 1 A). The neck-shaft angle was within normal limits (R146, L145; the normal range at the age of five years is 139 (+/-10) to 135 (+/-5)) in early adulthood. ( 21 ) Evidence of enamel hypoplasia, delayed tooth eruption, and potential malocclusion persisted, which may be attributable to her underlying XLH or influenced by other factors, such as hygiene and nutritional status. There were no issues with compliance, and no known side effects were observed. Patient 2. This 4-year, 3-month-old female presented to the clinic at 3.5 months of age with hypophosphatemia. Her mother had been diagnosed with XLH at the age of 2.5 years and had extremely short stature and bowlegs, achieving an adult height of 143 cm (-3.12 SDS) after conventional therapy. Biochemical testing revealed low serum phosphate and elevated alkaline phosphatase levels in the infant, but genetic testing was not performed because of parental refusal. Skeletal radiographic imaging confirmed the diagnosis of rickets. Conventional therapy was initiated at 3.5 months of age, and the patient was switched to burosumab therapy at seven months of age. Although high-dose burosumab (2 to 4.4 mg/kg) was administered, her serum phosphate levels remained persistently low, ranging from 2.46 to 3.97 mg/dL. Her alkaline phosphatase levels generally ranged from 254 to 363 U/L, with one transient elevation to 4100 U/L, which was attributed to spontaneously resolving hyperphosphatasemia in infancy. Growth deceleration was noted starting at 3.5 months of age (length SDS − 1.08 and weight SDS − 1.47). Upon the initiation of burosumab therapy, the patient’s body length was at an SDS of -2.56, with a weight SDS of -2.17. At 1.5 years of age, she exhibited growth faltering, with the nadir reaching an SDS of -3.38 for length and − 4.36 for weight. Despite ongoing treatment, there was no observable significant improvement in growth until the patient underwent adenoidectomy for obstructive sleep apnea at three years and nine months of age. There was a marked improvement in both height and weight following surgery. Skeletal features demonstrated a favorable outcome, as reflected by the RSS and MAD (Fig. 1 B), without femoral or tibial bowing. The neck-shaft angle was normal (R130, L132; normal range 140 ± 10 for age four years). ( 21 ) No dental abscesses or abnormalities were reported. Patient 3 This 22-month-old female presented shortly after birth and was prenatally diagnosed with a PHEX mutation through whole exome sequencing conducted at the parents' request, although there was no clinical indication. Postnatal blood tests revealed hypophosphatemia with normal alkaline phosphatase and calcium levels, providing biochemical evidence consistent with the diagnosis of XLH. Conventional therapy, including oral phosphate supplements and active vitamin D analogs (calcitriol), was initiated following the diagnosis. At seven months of age, the treatment was switched to burosumab, which was initiated at a dose of 10 mg (0.90 mg/kg) and subsequently increased to a maximum dose of 30 mg (2.50 mg/kg). The medication was administered at home by a nurse practitioner. After 15 months of burosumab treatment, her serum phosphate level remained below the sex- and age-specific reference range, despite high levels of dosing. At the age of 22 months, her growth was consistent, maintaining the 50th -75th percentile for length and above the 97th percentile for weight. Her knee RSS was + 1 after 15 months of burosumab treatment (at 22 months of age). Despite genu varum that looked physiological, no femoral or tibial bowing was noted, and the neck-shaft angle was normal (R144, L144; the normal range is 141 ± 10 at three years of age).( 21 ) She achieved the motor milestone of independent walking at 14 months of age, which is within the expected developmental window. She did not experience any known side effects of the medication and demonstrated excellent adherence to the treatment regimen. No dental issues have been reported to date. Discussion In this report, we describe three pediatric patients with XLH who began therapy during early infancy. Diagnosis through prenatal genetic testing or family history allows timely intervention, which enables prompt treatment initiation and likely contributes to improved growth and orthopedic outcomes. Impaired growth is a hallmark of XLH, with untreated patients typically showing normal birth length but experiencing growth stunting during infancy and childhood ( 22 ). The growth patterns of two of our patients followed the expected trajectory of linear growth during the first years of life. The third patient experienced growth faltering, which may be attributed to either sleep-disordered breathing, phosphate imbalance or a combination of the two. While both of those factors are plausible, the improvement in linear growth following adenotonsillectomy supports the hypothesis that sleep-disordered breathing most likely played a key role in her growth delay. Notably, growth faltering in XLH patients can result from multiple contributing factors that may not always be directly related to XLH itself, underscoring the importance of a comprehensive evaluation to guide effective management and optimize patient outcomes. Burosumab is approved for the treatment of XLH in patients aged six months and older in Israel and the United States. However, there are limited data on its efficacy in the youngest age groups, and further research is needed to determine the appropriate dosage, effectiveness, and safety in larger cohorts of infants. In our case series, the three patients received higher doses of burosumab than the guideline recommendations, motivated by treatment goals aimed at correcting their phosphate levels. However, as our understanding has progressed, the current therapeutic approach is to target clinical and radiological outcomes over normalizing phosphate levels. ( 23 ) Our series of three patients precludes our ability to provide any recommendations regarding dosage or underlying mechanisms, issues that warrant further investigation. Patients with XLH often experience bone deformities, such as lower extremity varus (bowed femurs and tibias, genu varum, and coxa vara), due to impaired phosphate metabolism and insufficient bone mineralization. These deformities can result in chronic pain, stunted growth, and mobility issues, which often require orthopedic interventions ( 17 ). In our case series, burosumab, which was initiated at six months of age, proved to be effective in managing XLH, with notable improvements in phosphate levels. Although bone pain was not assessed by a structured questionnaire, the parents of each of our patients reported improvements in their child's condition. Importantly, the two patients in whom the mechanical axis was assessable demonstrated neutral mechanical axis deviation, indicating improved lower limb alignment. This neutral axis supports the effectiveness of burosumab in enhancing skeletal health and preventing further deformities. Finally, long bone diaphyseal bowing and coxa vara did not develop following the early initiation of burosumab treatment in any of the patients in our series. Dental health issues were not reported in two of our patients, whereas one experienced dental complications despite early initiation of treatment with burosumab. This finding aligns with a previous report from our group that described a 5.5-year-old patient who sustained recurrent dental abscesses over three years of treatment with burosumab ( 24 ). Brener et al. postulated that dental morbidity in XLH patients may be influenced by additional PHEX -related local mineralization inhibitors, such as osteopontin. This hypothesis is supported by the persistence of unique dental morphology, including unusually large pulp dimensions, in patients receiving burosumab therapy ( 24 ). This variability may, however, reflect differences in individual genetic factors, adherence to oral hygiene practices, or compliance with supplement use. All patients received their injected medication at home from a nurse practitioner, ensuring high adherence to treatment. There were no reports of any significant side effects from burosumab, suggesting that the drug is generally well tolerated in infancy. However, ongoing monitoring for potential side effects is essential, particularly given the long-term nature of the treatment. The limitations of this case series include a small sample size, lack of a control group, individualized dosing regimens, a short follow-up period, and potential confounders in growth outcomes. To the best of our knowledge, this is the first study to publish on the use of burosumab in this young age group. The strengths of the study include the timely initiation of burosumab therapy, real-world data, comprehensive monitoring, and a multidisciplinary approach to care. Conclusion Our case series highlights the potential benefits of the initiation of burosumab treatment for XLH in early infancy by demonstrating improvements in growth, phosphate levels, and skeletal outcomes. While burosumab appears to be well tolerated, particularly in infancy, further research is needed to refine dosing strategies and assess the long-term safety and efficacy of burosumab in such young patients. Continued monitoring and individualized care are essential for optimizing outcomes and addressing the diverse needs of pediatric patients with XLH. Declarations Author contributions Authors RR prepared the first draft of the paper. Authors RR, AB, ND, RK, RR, EC, OB, AL, YL and LZ contributed to the experimental work. All the authors reviewed the paper critically for intellectual content. RR and YL addressed co-authors’ comments and revised the manuscript accordingly. All the authors approved the final version and are accountable for the work, ensuring the accuracy and integrity of the paper. Acknowledgments The authors thank all of the participating patients and their families and the multidisciplinary team that cares for XLH patients treated at the Metabolic Bone Clinic. We wish to thank Esther Eshkol for editorial assistance. Ethics statement The studies involving human participants were reviewed and approved by Tel Aviv Sourasky Medical Center (TLV-0041-19). Written informed consent to participate in this study was provided by the participants’ legal guardian. Consent for publication Informed consent for publication was obtained from the parents of all three patients included in this study. Declaration of conflicts of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. Authors RR, AB, YL, and LZ receive speaker fees, research funding, and travel grants from Medison Pharma. Authors RR and YL received advisory board compensation from Medison Pharma. Funding Kyowa Kirin Services Limited provided funding for the editorial support and open access fees (TLV – 250093). The funders played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. Data availability statement The raw data supporting the conclusions of this article will be made available by the authors without undue reservation. References Sandy JL, Nunez C, Wheeler BJ, et al. 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Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. Lancet . 2019;393(10189):2416-27. US Food and Drug Administration. Crysvita (burosumab-twza) Marketing Approval. Levy-Shraga Y, Levi S, Regev R, et al. Linear growth of children with X-linked hypophosphatemia treated with burosumab: a real-life observational study. Eur J Pediatr . 2023;182(11):5191-202. Ward LM, Hogler W, Glorieux FH, et al. Burosumab vs conventional therapy in children with X-linked hypophosphatemia: results of the open-label, phase 3 extension period. JBMR Plus . 2024;8(1):ziad001. Makitie O, Doria A, Kooh SW, et al. Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets. J Clin Endocrinol Metab . 2003;88(8):3591-7. Haffner D, Emma F, Eastwood DM, et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia. 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Sociodemographic, perinatal, genetic, and clinical characteristics of three infants with XLH Patient 1 5 y 2 mo ♀ Patient 2 4 y 3 mo ♀ Patient 3 1 yr 10 mo ♀ Demographic Ethnicity Sephardic/Ashkenazi Jewish Ashkenazi Jewish Ashkenazi Jewish Family member with XLH None Mother None Household Single parent, two children Two parent, three children Two parent, three children Parent education University degree High school diploma University degree Socioeconomic position (cluster, index) Medium (7, 0.723) Low (1, -1.940) High (8, 1.317) Perinatal history Pregnancy In vitro fertilization, dizygotic twins Spontaneous Spontaneous Maternal medical history None XLH GDM, Factor XI deficiency, Lynch syndrome, CMV-positive Mode of delivery Cesarean section, elective Cesarean section due to prolonged labor Cesarean section, elective Gestational age, weeks 35 + 5 38 38 + 4 Birth weight, grams 2686 2630 4015 Birth weight, %, z score 59 (0.22) 21 (-0.81) 98 (2.02) Perinatal course Uneventful Respiratory distress hospitalization in NICU; normal phosphate levels Born LGA no hypoglycemic episodes Genetic analysis Age at genetic diagnosis 19 days; biochemical confirmation CMA in amniocentesis PHEX mutation in 1 twin 3 months; maternal XLH and patient's low phosphate level Prenatal; whole exome sequencing Genetic alteration Not available Genetic testing not done De novo chrx:22208575 c.1601c>t p.pro534leu rs886041363 Clinical history Congenital malformation None None Ventricular septal defect Developmental milestones Normal Developmental delay Normal Other medical conditions Severe allergic reaction; unknown allergen, epi-pen Growth faltering; adenotonsillectomy. mild hearing loss Mild hearing loss Socioeconomic position by home address was analyzed via the Israel Central Bureau of Statistics’ Characterization and Classification of Statistical Areas. Neighborhoods or localities were categorized into 10 socioeconomic clusters, with 1 being the most deprived and 10 being the most affluent, which were grouped into low (1–4), medium (5–7), and high (8–10) categories. The socioeconomic index, ranging from -2.797 to 2.590, is based on 14 variables reflecting demographics, education, standard of living, and employment.(20) Table 2. Growth, metabolic, and skeletal characteristics at the initiation of therapy Patient 1 5 y 2 mo ♀ Petient 2 4 y 3 mo ♀ Patient 3 1 yr 10 mo ♀ Conventional therapy Age at initiation of conventional treatment 2.1 months 3.5 months 2 days Weight, kg %, z score 5.130 92 (1.42) 4.820 7 (-1.46) 3.730 91 (1.31) Length, cm %, z score 54.6 56 (0.16) 57.8 14 (-1.07) not done Wt-to-length, %, z score 92 (1.41) 15 (-1.03) Serum metabolic markers iFGF23, pg/mL (range 28-37) <21 87 Not done Calcium, mg/dL (range) 8.9 (7.2-10) 10.3 (9-11) 8.8 (8.5-10.5) Phosphorus, mg/dL 2.6 3.5 3.3 Creatinine, mg/dL 0.36 0.50 0.71 Alkaline phosphatase, U/L 402 (145-320) 626 (40-515) 234 (91-281) iPTH, pg/mL (normal range) 52.9 (16-87) 13.5 (12-65) 58 (14-53) 25-OH-vitamin D, nmol/L 52 92 29 1,25 dihydroxy vitamin D, pmol/L (normal range) 40.9 (20-79) 45.6 (47.8-190.3) 49.9 (37-158) Urine metabolic markers Calcium, mg/dL 1.9 1 0.7 Phosphate, mg/dL 14.7 46 258.5 Creatinine, mg/dL 9 9 89.2 TRP % 77.4 27 37.7 TMP/GFR mg/dL 2.00 0.94 1.25 Burosumab therapy Age at initiation 6 months 7 months 7 months Dose at initiation, mg 10 (1.3 mg/kg) 10 (1.6 mg/kg) 10 (0.9 mg/kg) Maximal dose, mg 30 (2 mg/kg) 30 (4.4 mg/kg) 30 (2.5 mg/kg) Weight, kg %, z score 7.445 67 (0.44) 6.130 3 (-1.90) 10.800 100 (+2.80) Length, cm %, z score 65.6 65 (0.40) 60.7 0 (-2.96) 69 82 (+0.90) Weight-to-length %, z score 63 (0.34) 56 (0.14) 100 (+3.18) Serum metabolic markers Calcium, mg/dL (range) 9.4 (7.4-11.7) 10.2 (8.5-10.5) 10.3 (8.5-10.5) Phosphate, mg/dL 3.4 2.38 2.2 Creatinine, mg/dL 0.13 0.22 0.37 Alkaline phosphatase, U/L 536 (124-341) 647 (121.7-472.6) 474 (137-535) PTH, pg/mL 36.6 (6.7-38.8) 27.3 (12-65) 83 (14-53) 25-OH-vitamin D, nmol/L 38 77 127 1,25 dihydroxy vitamin D, pmol/L (normal range) 63.4 (20-79) 45.6 (48-240) 135 (37-158) Urine metabolic markers Calcium, mg/dL 1.81 2.8 Phosphate, mg/dL 31.3 4.5 41.8 Creatinine, mg/dL 8.7 4 59.3 TRP % 86.24 89.6 88 TMP/GFR mg/dL 2.93 2.13 6 Renal ultrasound Normal at 5 yrs Normal at 3 yrs 9 mo Normal at 1 yr Dental morbidity Complete primary dentition with an open bite and deep grooves on molars No complications No complications iFGF23, intact fibroblast growth factor 23; iPTH, intact parathyroid hormone; TRP, total reabsorption of phosphate; TmP/GFR, tubular maximum transport of phosphate to the glomerular filtration rate Table 3. Skeletal health and alignment: Rickets Severity Score and mechanical axis deviation in XLH patients Variable Patient 1 5 yr 2 mo ♀ Patient 2 4 year 3 mo ♀ Patient 3 1 yr 10 mo ♀ Duration of burosumab treatment 4 yrs and 7 mo 3 yrs 3 mo 1 yr 3 mo RSS at last assessment 0.5 1.0 1 Mechanical axis deviation Rt 0, Lt 0, Zone neutral Rt 0, Lt 0, Zone neutral not relevant Cite Share Download PDF Status: Published Journal Publication published 08 Jan, 2026 Read the published version in Orphanet Journal of Rare Diseases → Version 1 posted Editorial decision: Major revision 14 May, 2025 Reviewers agreed at journal 26 Apr, 2025 Reviewers invited by journal 25 Apr, 2025 Editor assigned by journal 08 Apr, 2025 First submitted to journal 06 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Regev","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYFADZgbGB0CKh48ELczMBiAtbKRYwyYBoghqMW9vv/iYh+GevMFx/mOVX3PsZNgYmB8+uoFHi8yZM8XGPAzFhhsOM7Pdlt2WDHQYm7FxDh4tEhI5aZIzGBIYZzYDtUhuYwZq4WGTxqtF/k36T6AWe5CWYslt9URokWA/xvCBISGxn5mZjfHjtsNEaOHJYZb4YJCQDNRiLM247TgPGzMhv7Aff/ghoSLBto3/4MOPP7dV2/OzNz98jE8LMO6AEWgAYTLzgEm8ykGA/QGcyfiDoOpRMApGwSgYiQAAwV87k5Kx4UYAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-0846-733X","institution":"Dana-Dwek Children's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ravit","middleName":"","lastName":"Regev","suffix":""},{"id":448068474,"identity":"ec03df6a-6884-4b8a-bcc6-0f0207c7fb42","order_by":1,"name":"Avivit Brener","email":"","orcid":"","institution":"Dana-Dwek Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Avivit","middleName":"","lastName":"Brener","suffix":""},{"id":448068475,"identity":"14348d35-5da4-4637-9947-a872854e5703","order_by":2,"name":"Nitzan Dror","email":"","orcid":"","institution":"Meir Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Nitzan","middleName":"","lastName":"Dror","suffix":""},{"id":448068476,"identity":"ceacdb3d-03fe-407e-b418-d9e5ae0998c9","order_by":3,"name":"Raphael Krespi","email":"","orcid":"","institution":"Dana-Dwek Children's Hospital Pediatric Orthopedics Department","correspondingAuthor":false,"prefix":"","firstName":"Raphael","middleName":"","lastName":"Krespi","suffix":""},{"id":448068477,"identity":"fa09fa0b-4c62-44d9-babc-43c4af2d66a7","order_by":4,"name":"Rebeca Rapalino","email":"","orcid":"","institution":"Tel Aviv Ichilov-Sourasky Medical Center: Tel Aviv Sourasky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Rebeca","middleName":"","lastName":"Rapalino","suffix":""},{"id":448068478,"identity":"47b3f135-6fcc-4c8d-86b2-8a6f9cfc9793","order_by":5,"name":"Efrat Chorna","email":"","orcid":"","institution":"Dana-Dwek Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Efrat","middleName":"","lastName":"Chorna","suffix":""},{"id":448068479,"identity":"df5205ba-203f-407a-93b8-e0474a6735d2","order_by":6,"name":"Ophir Borger","email":"","orcid":"","institution":"Dana-Dwek Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ophir","middleName":"","lastName":"Borger","suffix":""},{"id":448068480,"identity":"50c4227e-583a-4206-bfd5-82c9d6f8cc06","order_by":7,"name":"Adar Lopez","email":"","orcid":"","institution":"Dana-Dwek Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Adar","middleName":"","lastName":"Lopez","suffix":""},{"id":448068481,"identity":"1b125948-4392-4335-976b-5591ca7b0b50","order_by":8,"name":"Yael Lebenthal","email":"","orcid":"","institution":"Dana-Dwek Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yael","middleName":"","lastName":"Lebenthal","suffix":""},{"id":448068482,"identity":"2f234394-abaa-4e35-8938-2606059401a5","order_by":9,"name":"Leonid Zeitlin","email":"","orcid":"","institution":"Dana-Dwek Children's Hospital Pediatric Orthopedics Department","correspondingAuthor":false,"prefix":"","firstName":"Leonid","middleName":"","lastName":"Zeitlin","suffix":""}],"badges":[],"createdAt":"2025-04-06 08:24:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6385587/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6385587/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s13023-025-04177-2","type":"published","date":"2026-01-08T15:57:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":82137547,"identity":"a8aef2ac-0281-4207-9455-c1c8fc119d56","added_by":"auto","created_at":"2025-05-07 06:18:39","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":57212,"visible":true,"origin":"","legend":"\u003cp\u003eMechanical Axis Deviation (MAD) in patients treated with burosumab.\u003c/p\u003e\n\u003cp\u003ePanel a: Patient 1, neutral MAD after 4.6 years of burosumab treatment.\u003c/p\u003e\n\u003cp\u003ePanel b: Patient 2, neutral MAD after 3 years of burosumab treatment.\u003c/p\u003e\n\u003cp\u003eThese radiographic images show the mechanical axis (highlighted by yellow lines) in two patients, demonstrating successful correction of lower limb alignment following burosumab treatment.\u003c/p\u003e","description":"","filename":"figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6385587/v1/6acdfcf500a5193856c56804.jpg"},{"id":100069820,"identity":"b66e996d-e0ff-40c7-b53e-78e09381e806","added_by":"auto","created_at":"2026-01-12 16:15:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":834701,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6385587/v1/980bc0c7-5d3a-49b7-ae43-de7a90885700.pdf"}],"financialInterests":"","formattedTitle":"Burosumab in infants with X-linked hypophosphatemic rickets: a case series","fulltext":[{"header":"Plain language summary","content":"\u003cp\u003eThis case series followed three infants with X-linked hypophosphatemic rickets (XLH) who initiated burosumab treatment at 6 months of age, filling a significant knowledge gap in early intervention. Despite requiring higher-than-recommended dosing, burosumab demonstrated favorable outcomes in terms of growth parameters and skeletal development over a minimum one-year follow-up. Two patients maintained normal growth trajectories, whereas one experienced temporary growth faltering, which resolved after adenoidectomy. Importantly, neutral mechanical axis deviation was achieved, indicating effective prevention of lower limb deformities. No significant adverse effects were observed. Despite limitations such as a small sample size and short follow-up, these findings suggest that early burosumab therapy can improve outcomes in infantile XLH patients. Further research is needed to refine dosing protocols and assess long-term safety and efficacy in this young population.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003eX-linked hypophosphatemic rickets (XLH) is a rare inherited progressive metabolic bone disorder with an estimated prevalence of 1.3\u0026ndash;4.8 cases per 100,000 individuals.(\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) XLH results from a mutation in the phosphate-regulating endopeptidase homolog on the X chromosome (\u003cem\u003ePHEX\u003c/em\u003e) gene, leading to excess fibroblast growth factor 23 (FGF23). This mutation causes renal phosphate wasting and insufficient production of 1,25-dihydroxyvitamin D (1,25(OH)2D), resulting in reduced intestinal phosphate absorption and, ultimately, hypophosphatemia.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) Children with XLH exhibit skeletal characteristics of rickets and osteomalacia, including progressive bowing deformities of the lower limbs, disproportionate short stature, bone pain, dental abscesses, and proximal muscle weakness, all of which impair physical function and diminish quality of life. (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eSince the 1980s, individuals with XLH have been treated with multiple daily doses of oral phosphate and active vitamin D. While this conventional therapy can improve clinical features, it carries risks, such as nephrocalcinosis and hyperparathyroidism, and can be burdensome due to frequent dosing, gastrointestinal side effects, and the need for careful monitoring. (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) In April 2018, burosumab, a human monoclonal antibody against FGF23, received FDA approval in the USA and conditional approval in Europe for the treatment of children with XLH aged over one year, as well as adolescents with growing skeletons.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) In 2020, the Israeli Ministry of Health approved burosumab for children with XLH older than one year of age. A phase three international multicenter trial demonstrated that burosumab is superior to conventional therapy for improving rickets scores, growth, limb deformities, and mobility in children aged 1\u0026ndash;12 years.(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e) This was supported by real-world evidence that reportedly holds promise for improvements in linear growth, rickets scores, and laboratory metrics in pediatric patients treated with burosumab.(\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) In 2022, the FDA extended its approval to children as young as six months of age.(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) Data on improvements in linear growth and biochemical markers with burosumab treatment initiated before the age of one year, however, are limited. Makite et al. demonstrated that starting conventional treatment before the age of one year leads to better rickets scores in patients with XLH, although it does not completely normalize skeletal development.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) This case series describes three patients with XLH who began burosumab therapy in infancy and were followed for at least one year, with a focus on its impact on linear growth, the rickets score, and laboratory parameters in real-life settings.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003e Three infants with XLH followed at the Metabolic Bone Clinic at Dana-Dwek Children\u0026rsquo;s Hospital, Tel Aviv Sourasky Medical Center, and the Endocrine Unit at Meir Medical Center began burosumab treatment before the age of one year. Routine care at our centers included in-clinic visits every three to six months during which anthropometric measurements were performed along with evaluations of metabolic laboratory parameters. Medical interviews were conducted to assess treatment adherence and efficacy and to monitor any adverse effects. Skeletal radiographs were obtained every 6 to 12 months to assess the severity of rickets as part of routine clinical care. Individualized treatment plans were based upon a composite evaluation of these clinical parameters.\u003c/p\u003e \u003cp\u003e The three patients were started on conventional therapy with oral phosphate and active vitamin D shortly after diagnosis, in accordance with standard XLH treatment guidelines. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) Conventional therapy was discontinued seven days before the initiation of burosumab, which was administered at a dose of 0.8 mg/kg of body weight, rounded to the nearest 10 mg according to the protocol. (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). The dosage was gradually adjusted on the basis of laboratory results, in accordance with practice guidelines.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) Clinical characteristics, biochemical markers, findings on skeletal radiographs, and growth parameters were collected and analyzed.\u003c/p\u003e \u003cp\u003eWeight was measured with a tabletop electronic infant scale with an attached measuring rod (Model 374\u0026thinsp;+\u0026thinsp;Measuring Rod 233, SECA, Gmbh \u0026amp; Co., Germany), and crown-heel length was measured with the infant in the supine position. The World Health Organization (WHO) Growth Standards were used for infants 0 to two years of age, and z-scores were tallied. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) The weight-to-length ratio was calculated as an indicator of weight status in children younger than two years of age. (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) Body mass index (BMI) of older children was calculated by dividing body weight in kilograms by height in meters squared, and height, weight, and BMI z-scores were determined using sex- and age-specific CDC 2000 growth charts. (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eLaboratory blood samples were collected prior to burosumab injections and analyzed for serum levels of phosphorus, calcium, creatinine, alkaline phosphatase (ALP), 25-hydroxy vitamin D, 1,25-dihydroxyvitamin D (1,25 vit D), intact parathyroid hormone (PTH), and intact FGF23. Spot urine tests were performed to measure phosphorus, calcium, and creatinine levels. Total reabsorption of phosphate (TRP) was calculated by mean of an online calculator and is presented as a percentage. (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) The tubular maximum transport of the phosphate-to-glomerular filtration rate (TmP/GFR) was calculated from values in serum and spot urine as previously described elsewhere. (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e) Skeletal radiographs were obtained as needed for routine clinical care and evaluated by two independent bone health specialists (RR and LZ) who used the Thacher Rickets Severity Score (RSS). The images were scored on a scale from 0 to 6, with higher scores indicating greater severity of rickets. The mechanical axis of the lower limb, also referred to as the Mikulicz line, was determined by drawing a line from the center of the femoral head to the center of the ankle. Under normal conditions, this axis passes approximately 8 mm medial to the midpoint of the knee. Deviations from this range signify alignment abnormalities. Specifically, an axis that shifts laterally indicates valgus alignment, whereas a medial shift suggests varus alignment. The extent of this deviation is termed the mechanical axis deviation (MAD) (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). The femoral neck angle, a radiological measurement that refers to the angle formed between the axis of the femoral neck and the axis of the femoral shaft (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e), was assessed by a pediatric orthopedist.\u003c/p\u003e \u003cp\u003eSocioeconomic position by home address was analyzed using the Israel Central Bureau of Statistics\u0026rsquo; Characterization and Classification of Statistical Areas. Neighborhoods or localities were categorized into 10 socioeconomic clusters, with 1 being the most deprived and 10 being the most affluent, which were grouped into low (\u003cspan additionalcitationids=\"CR2 CR3\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), medium (\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), and high (\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) categories. The socioeconomic index, ranging from \u0026minus;\u0026thinsp;2.797 to 2.590, is based upon 14 variables reflecting demographics, education, standard of living, and employment.(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e)\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eCase series\u003c/h2\u003e \u003cp\u003e \u003cb\u003ePatient 1.\u003c/b\u003e This 5-year 2-month-old female presented to our clinic shortly after birth. She was born preterm at 35\u0026thinsp;+\u0026thinsp;5 weeks of gestation, with a birth weight appropriate for gestational age (2.685 kg), as one of a pair of twins. Prenatal genetic testing via amniocentesis identified a \u003cem\u003ePHEX\u003c/em\u003e mutation, although it was initially unclear which twin was affected. At 19 days of age, the patient was hospitalized for neonatal fever, during which blood tests revealed hypophosphatemia, establishing the diagnosis of XLH. Conventional treatment with phosphate supplements and calcitriol was initiated at 2 months of age. At 6 months, burosumab therapy was started at a dose of 10 mg (1.38 mg/kg), was administered at home by a nurse practitioner, and was titrated to a maximum of 40 mg (2.22 mg/kg). Despite this high-dose burosumab regimen, serum phosphate levels remained below the lower limit of normal for age and sex. At the age of 5 years, growth remained stable, with height consistently measuring between the 10th and 25th percentiles and weight at the 50th percentile (BMI between the 85th and 90th percentiles). The patient's mother reported significant improvement in bone pain and physical activity, although some residual musculoskeletal discomfort persisted. The skeletal outcomes showed a favorable RSS and neutral MAD without femoral bowing and with only mild tibial bowing (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). The neck-shaft angle was within normal limits (R146, L145; the normal range at the age of five years is 139 (+/-10) to 135 (+/-5)) in early adulthood. (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) Evidence of enamel hypoplasia, delayed tooth eruption, and potential malocclusion persisted, which may be attributable to her underlying XLH or influenced by other factors, such as hygiene and nutritional status. There were no issues with compliance, and no known side effects were observed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003ePatient 2.\u003c/b\u003e This 4-year, 3-month-old female presented to the clinic at 3.5 months of age with hypophosphatemia. Her mother had been diagnosed with XLH at the age of 2.5 years and had extremely short stature and bowlegs, achieving an adult height of 143 cm (-3.12 SDS) after conventional therapy. Biochemical testing revealed low serum phosphate and elevated alkaline phosphatase levels in the infant, but genetic testing was not performed because of parental refusal. Skeletal radiographic imaging confirmed the diagnosis of rickets. Conventional therapy was initiated at 3.5 months of age, and the patient was switched to burosumab therapy at seven months of age. Although high-dose burosumab (2 to 4.4 mg/kg) was administered, her serum phosphate levels remained persistently low, ranging from 2.46 to 3.97 mg/dL. Her alkaline phosphatase levels generally ranged from 254 to 363 U/L, with one transient elevation to 4100 U/L, which was attributed to spontaneously resolving hyperphosphatasemia in infancy. Growth deceleration was noted starting at 3.5 months of age (length SDS \u0026minus;\u0026thinsp;1.08 and weight SDS \u0026minus;\u0026thinsp;1.47). Upon the initiation of burosumab therapy, the patient\u0026rsquo;s body length was at an SDS of -2.56, with a weight SDS of -2.17. At 1.5 years of age, she exhibited growth faltering, with the nadir reaching an SDS of -3.38 for length and \u0026minus;\u0026thinsp;4.36 for weight. Despite ongoing treatment, there was no observable significant improvement in growth until the patient underwent adenoidectomy for obstructive sleep apnea at three years and nine months of age. There was a marked improvement in both height and weight following surgery. Skeletal features demonstrated a favorable outcome, as reflected by the RSS and MAD (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB), without femoral or tibial bowing. The neck-shaft angle was normal (R130, L132; normal range 140\u0026thinsp;\u0026plusmn;\u0026thinsp;10 for age four years). (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) No dental abscesses or abnormalities were reported.\u003c/p\u003e \u003cp\u003e \u003cb\u003ePatient 3\u003c/b\u003e This 22-month-old female presented shortly after birth and was prenatally diagnosed with a \u003cem\u003ePHEX\u003c/em\u003e mutation through whole exome sequencing conducted at the parents' request, although there was no clinical indication. Postnatal blood tests revealed hypophosphatemia with normal alkaline phosphatase and calcium levels, providing biochemical evidence consistent with the diagnosis of XLH. Conventional therapy, including oral phosphate supplements and active vitamin D analogs (calcitriol), was initiated following the diagnosis. At seven months of age, the treatment was switched to burosumab, which was initiated at a dose of 10 mg (0.90 mg/kg) and subsequently increased to a maximum dose of 30 mg (2.50 mg/kg). The medication was administered at home by a nurse practitioner. After 15 months of burosumab treatment, her serum phosphate level remained below the sex- and age-specific reference range, despite high levels of dosing. At the age of 22 months, her growth was consistent, maintaining the 50th -75th percentile for length and above the 97th percentile for weight. Her knee RSS was +\u0026thinsp;1 after 15 months of burosumab treatment (at 22 months of age). Despite genu varum that looked physiological, no femoral or tibial bowing was noted, and the neck-shaft angle was normal (R144, L144; the normal range is 141\u0026thinsp;\u0026plusmn;\u0026thinsp;10 at three years of age).(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) She achieved the motor milestone of independent walking at 14 months of age, which is within the expected developmental window. She did not experience any known side effects of the medication and demonstrated excellent adherence to the treatment regimen. No dental issues have been reported to date.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this report, we describe three pediatric patients with XLH who began therapy during early infancy. Diagnosis through prenatal genetic testing or family history allows timely intervention, which enables prompt treatment initiation and likely contributes to improved growth and orthopedic outcomes.\u003c/p\u003e \u003cp\u003eImpaired growth is a hallmark of XLH, with untreated patients typically showing normal birth length but experiencing growth stunting during infancy and childhood (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). The growth patterns of two of our patients followed the expected trajectory of linear growth during the first years of life. The third patient experienced growth faltering, which may be attributed to either sleep-disordered breathing, phosphate imbalance or a combination of the two. While both of those factors are plausible, the improvement in linear growth following adenotonsillectomy supports the hypothesis that sleep-disordered breathing most likely played a key role in her growth delay. Notably, growth faltering in XLH patients can result from multiple contributing factors that may not always be directly related to XLH itself, underscoring the importance of a comprehensive evaluation to guide effective management and optimize patient outcomes.\u003c/p\u003e \u003cp\u003e Burosumab is approved for the treatment of XLH in patients aged six months and older in Israel and the United States. However, there are limited data on its efficacy in the youngest age groups, and further research is needed to determine the appropriate dosage, effectiveness, and safety in larger cohorts of infants. In our case series, the three patients received higher doses of burosumab than the guideline recommendations, motivated by treatment goals aimed at correcting their phosphate levels. However, as our understanding has progressed, the current therapeutic approach is to target clinical and radiological outcomes over normalizing phosphate levels. (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) Our series of three patients precludes our ability to provide any recommendations regarding dosage or underlying mechanisms, issues that warrant further investigation.\u003c/p\u003e \u003cp\u003ePatients with XLH often experience bone deformities, such as lower extremity varus (bowed femurs and tibias, genu varum, and coxa vara), due to impaired phosphate metabolism and insufficient bone mineralization. These deformities can result in chronic pain, stunted growth, and mobility issues, which often require orthopedic interventions (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). In our case series, burosumab, which was initiated at six months of age, proved to be effective in managing XLH, with notable improvements in phosphate levels. Although bone pain was not assessed by a structured questionnaire, the parents of each of our patients reported improvements in their child's condition. Importantly, the two patients in whom the mechanical axis was assessable demonstrated neutral mechanical axis deviation, indicating improved lower limb alignment. This neutral axis supports the effectiveness of burosumab in enhancing skeletal health and preventing further deformities. Finally, long bone diaphyseal bowing and coxa vara did not develop following the early initiation of burosumab treatment in any of the patients in our series.\u003c/p\u003e \u003cp\u003eDental health issues were not reported in two of our patients, whereas one experienced dental complications despite early initiation of treatment with burosumab. This finding aligns with a previous report from our group that described a 5.5-year-old patient who sustained recurrent dental abscesses over three years of treatment with burosumab (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Brener et al. postulated that dental morbidity in XLH patients may be influenced by additional \u003cem\u003ePHEX\u003c/em\u003e-related local mineralization inhibitors, such as osteopontin. This hypothesis is supported by the persistence of unique dental morphology, including unusually large pulp dimensions, in patients receiving burosumab therapy (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). This variability may, however, reflect differences in individual genetic factors, adherence to oral hygiene practices, or compliance with supplement use.\u003c/p\u003e \u003cp\u003eAll patients received their injected medication at home from a nurse practitioner, ensuring high adherence to treatment. There were no reports of any significant side effects from burosumab, suggesting that the drug is generally well tolerated in infancy. However, ongoing monitoring for potential side effects is essential, particularly given the long-term nature of the treatment.\u003c/p\u003e \u003cp\u003eThe limitations of this case series include a small sample size, lack of a control group, individualized dosing regimens, a short follow-up period, and potential confounders in growth outcomes. To the best of our knowledge, this is the first study to publish on the use of burosumab in this young age group. The strengths of the study include the timely initiation of burosumab therapy, real-world data, comprehensive monitoring, and a multidisciplinary approach to care.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eOur case series highlights the potential benefits of the initiation of burosumab treatment for XLH in early infancy by demonstrating improvements in growth, phosphate levels, and skeletal outcomes. While burosumab appears to be well tolerated, particularly in infancy, further research is needed to refine dosing strategies and assess the long-term safety and efficacy of burosumab in such young patients. Continued monitoring and individualized care are essential for optimizing outcomes and addressing the diverse needs of pediatric patients with XLH.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors RR prepared the first draft of the paper. Authors RR, AB, ND, RK, RR, EC, OB, AL, YL and LZ contributed to the experimental work. All the authors reviewed the paper critically for intellectual content. RR and YL addressed co-authors\u0026rsquo; comments and revised the manuscript accordingly. All the authors approved the final version and are accountable for the work, ensuring the accuracy and integrity of the paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank all of the participating patients and their families and the multidisciplinary team that cares for XLH patients treated at the Metabolic Bone Clinic. We wish to thank Esther Eshkol for editorial assistance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe studies involving human participants were reviewed and approved by Tel Aviv Sourasky Medical Center (TLV-0041-19). Written informed consent to participate in this study was provided by the participants\u0026rsquo; legal guardian.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent for publication was obtained from the parents of all three patients included in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003econflicts\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest. Authors RR, AB, YL, and LZ receive speaker fees, research funding, and travel grants from Medison Pharma.\u003c/p\u003e\n\u003cp\u003eAuthors RR and YL received advisory board compensation from Medison Pharma.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKyowa Kirin Services Limited provided funding for the editorial support and open access fees (TLV \u0026ndash; 250093). The funders played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe raw data supporting the conclusions of this article will be made available by the authors without undue reservation.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSandy JL, Nunez C, Wheeler BJ, et al. Prevalence and characteristics of paediatric X-linked hypophosphataemia in Australia and New Zealand: Results from the Australian and the New Zealand Paediatric Surveillance Units survey. \u003cem\u003eBone\u003c/em\u003e. 2023;173:116791.\u003c/li\u003e\n\u003cli\u003eHawley S, Shaw NJ, Delmestri A, et al. Prevalence and Mortality of Individuals With X-Linked Hypophosphatemia: A United Kingdom Real-World Data Analysis. \u003cem\u003eJ Clin Endocrinol Metab\u003c/em\u003e. 2020;105(3):e871-8.\u003c/li\u003e\n\u003cli\u003eRafaelsen S, Johansson S, Raeder H, et al. Hereditary hypophosphatemia in Norway: a retrospective population-based study of genotypes, phenotypes, and treatment complications. \u003cem\u003eEur J Endocrinol\u003c/em\u003e. 2016;174(2):125-36.\u003c/li\u003e\n\u003cli\u003eHo BB, Bergwitz C. FGF23 signalling and physiology. \u003cem\u003eJ Mol Endocrinol\u003c/em\u003e. 2021;66(2):R23-R32.\u003c/li\u003e\n\u003cli\u003eBaroncelli GI, Mora S. X-Linked Hypophosphatemic Rickets: Multisystemic Disorder in Children Requiring Multidisciplinary Management. \u003cem\u003eFront Endocrinol (Lausanne)\u003c/em\u003e. 2021;12:688309.\u003c/li\u003e\n\u003cli\u003eImel EA, Glorieux FH, Whyte MP, et al. Burosumab versus conventional therapy in children with X-linked hypophosphataemia: a randomised, active-controlled, open-label, phase 3 trial. \u003cem\u003eLancet\u003c/em\u003e. 2019;393(10189):2416-27.\u003c/li\u003e\n\u003cli\u003eUS Food and Drug Administration. Crysvita (burosumab-twza) Marketing Approval.\u003c/li\u003e\n\u003cli\u003eLevy-Shraga Y, Levi S, Regev R, et al. Linear growth of children with X-linked hypophosphatemia treated with burosumab: a real-life observational study. \u003cem\u003eEur J Pediatr\u003c/em\u003e. 2023;182(11):5191-202.\u003c/li\u003e\n\u003cli\u003eWard LM, Hogler W, Glorieux FH, et al. Burosumab vs conventional therapy in children with X-linked hypophosphatemia: results of the open-label, phase 3 extension period. \u003cem\u003eJBMR Plus\u003c/em\u003e. 2024;8(1):ziad001.\u003c/li\u003e\n\u003cli\u003eMakitie O, Doria A, Kooh SW, et al. Early treatment improves growth and biochemical and radiographic outcome in X-linked hypophosphatemic rickets. \u003cem\u003eJ Clin Endocrinol Metab\u003c/em\u003e. 2003;88(8):3591-7.\u003c/li\u003e\n\u003cli\u003eHaffner D, Emma F, Eastwood DM, et al. Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia. \u003cem\u003eNat Rev Nephrol\u003c/em\u003e. 2019;15(7):435-55.\u003c/li\u003e\n\u003cli\u003eUltragenyx Pharmaceutical Inc. Dosing for Children | Crysvita HCP. 2024.\u003c/li\u003e\n\u003cli\u003eUltragenyx Pharmaceutical Inc. Crysvita Full Prescribing Information. 2024.\u003c/li\u003e\n\u003cli\u003eChou JH, Roumi S, Rajesh R. PediTools Electronic Growth Chart Calculators: Applications in Clinical Care, Research, and Quality Improvement. \u003cem\u003eJ Med Internet Res\u003c/em\u003e. 2020;22(1):e16204.\u003c/li\u003e\n\u003cli\u003eFreedman DS, Sharma AJ, Hamner HC, et al. Trends in Weight-for-Length Among Infants in WIC From 2000 to 2014. \u003cem\u003ePediatrics\u003c/em\u003e. 2017;139(1).\u003c/li\u003e\n\u003cli\u003eBMI reference.pdf.\u003c/li\u003e\n\u003cli\u003eGPN. TMP-GFR Calculator.\u003c/li\u003e\n\u003cli\u003ePayne RB. Renal tubular reabsorption of phosphate (TmP/GFR): indications and interpretation. \u003cem\u003eAnn Clin Biochem\u003c/em\u003e. 1998;35(2):201-6.\u003c/li\u003e\n\u003cli\u003ePaley D, Herzenberg JE, Tetsworth K, et al. Deformity Planning for Frontal and Sagittal Plane Corrective Osteotomies. \u003cem\u003eOrthop Clin North Am\u003c/em\u003e. 1994;25(3):425-65.\u003c/li\u003e\n\u003cli\u003eIsrael Central Bureau of Statistics. Characterization and Classification of Geographical Units by the Socio-Economic Level of the Population, 2015. 2020.\u003c/li\u003e\n\u003cli\u003eVan Geel P, Cools W, Laumen A. Evolution of head-shaft angle and neck-shaft angle in childhood. \u003cem\u003eActa Orthop Belg\u003c/em\u003e. 2021;87(3):435-41.\u003c/li\u003e\n\u003cli\u003eKamenicky P, Briot K, Munns CF, et al. X-linked hypophosphataemia. \u003cem\u003eLancet\u003c/em\u003e. 2024;404(10455):887-901.\u003c/li\u003e\n\u003cli\u003eWalker EYX, Lindsay TAJ, Allgrove J, et al. Burosumab in management of X-linked hypophosphataemia: a retrospective cohort study of growth and serum phosphate levels. \u003cem\u003eArch Dis Child\u003c/em\u003e. 2023;108(5):379-84.\u003c/li\u003e\n\u003cli\u003eBrener R, Zeitlin L, Lebenthal Y, et al. Dental health of pediatric patients with X-linked hypophosphatemia (XLH) after three years of burosumab therapy. \u003cem\u003eFront Endocrinol (Lausanne)\u003c/em\u003e. 2022;13:947814\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Sociodemographic, perinatal, genetic, and clinical characteristics of three infants with XLH\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"917\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e5 y 2 mo ♀\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4 y 3 mo ♀\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 3\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e1 yr 10 mo ♀\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 917px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDemographic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eEthnicity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eSephardic/Ashkenazi Jewish\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eAshkenazi Jewish\u003cbr\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eAshkenazi Jewish\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eFamily member with XLH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eMother\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eHousehold\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eSingle parent, two children\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eTwo parent, three children\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eTwo parent, three children\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eParent education\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eUniversity degree\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eHigh school diploma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eUniversity degree\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eSocioeconomic position (cluster, index)\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eMedium (7, 0.723)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eLow (1, -1.940)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eHigh (8, 1.317)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 917px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePerinatal history\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003ePregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eIn vitro fertilization, dizygotic twins\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eSpontaneous\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eSpontaneous\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eMaternal medical history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eXLH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eGDM, Factor XI deficiency, Lynch syndrome, CMV-positive\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eMode of delivery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eCesarean section, elective\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eCesarean section due to prolonged labor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eCesarean section, elective\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eGestational age, weeks\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e35 + 5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e38 + 4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eBirth weight, grams\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e2686\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e2630\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e4015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eBirth weight, %, z score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e59 (0.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e21 (-0.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e98 (2.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003ePerinatal course\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eUneventful\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eRespiratory distress hospitalization in NICU; normal phosphate levels\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eBorn LGA\u003cbr\u003e\u0026nbsp;no hypoglycemic episodes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 917px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGenetic analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 274px;\"\u003e\n \u003cp\u003eAge at genetic diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003e19 days;\u0026nbsp;\u003cbr\u003e\u0026nbsp;biochemical confirmation\u003c/p\u003e\n \u003cp\u003eCMA in amniocentesis\u0026nbsp;\u003cbr\u003e\u003cem\u003ePHEX\u003c/em\u003e mutation in 1 twin\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003e3 months;\u003cbr\u003e\u0026nbsp;maternal XLH and patient\u0026apos;s low phosphate level\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003ePrenatal;\u003c/p\u003e\n \u003cp\u003ewhole exome sequencing\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 274px;\"\u003e\n \u003cp\u003eGenetic alteration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eNot available\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eGenetic testing not done\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eDe novo chrx:22208575\u0026nbsp;c.1601c\u0026gt;t\u0026nbsp;p.pro534leu\u0026nbsp;rs886041363\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 917px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eClinical history\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eCongenital malformation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eNone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eVentricular septal defect\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eDevelopmental milestones\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eDevelopmental delay\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eNormal\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 274px;\"\u003e\n \u003cp\u003eOther medical conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eSevere allergic reaction;\u0026nbsp;\u003cbr\u003e\u0026nbsp;unknown allergen, epi-pen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eGrowth faltering; adenotonsillectomy.\u003c/p\u003e\n \u003cp\u003emild hearing loss\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 214px;\"\u003e\n \u003cp\u003eMild hearing loss\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eSocioeconomic position by home address was analyzed via the Israel Central Bureau of Statistics\u0026rsquo; Characterization and Classification of Statistical Areas. Neighborhoods or localities were categorized into 10 socioeconomic clusters, with 1 being the most deprived and 10 being the most affluent, which were grouped into low (1\u0026ndash;4), medium (5\u0026ndash;7), and high (8\u0026ndash;10) categories. The socioeconomic index, ranging from -2.797 to 2.590, is based on 14 variables reflecting demographics, education, standard of living, and employment.(20)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u003c/strong\u003e Growth, metabolic, and skeletal characteristics at the initiation of therapy\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"775\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e5 y 2 mo ♀\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePetient 2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4 y 3 mo ♀\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 3\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e1 yr 10 mo ♀\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 775px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eConventional therapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eAge at initiation of conventional treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e2.1 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e3.5 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e2 days\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eWeight, kg\u003c/p\u003e\n \u003cp\u003e%, z score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e5.130\u0026nbsp;\u003cbr\u003e\u0026nbsp;92 (1.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e4.820\u0026nbsp;\u003cbr\u003e\u0026nbsp;7 (-1.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e3.730\u0026nbsp;\u003cbr\u003e\u0026nbsp;91 (1.31)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eLength, cm\u003c/p\u003e\n \u003cp\u003e%, z score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e54.6\u003c/p\u003e\n \u003cp\u003e56 (0.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e57.8\u003c/p\u003e\n \u003cp\u003e14 (-1.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003enot done\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eWt-to-length, %, z score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e92 (1.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e15 (-1.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 775px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum metabolic markers\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eiFGF23, pg/mL (range 28-37)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026lt;21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003eNot done\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eCalcium, mg/dL (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e8.9 (7.2-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e10.3 (9-11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e8.8 (8.5-10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003ePhosphorus, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e3.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eCreatinine, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e0.36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eAlkaline phosphatase, U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e402 (145-320)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e626 (40-515)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e234 (91-281)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eiPTH, pg/mL (normal range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e52.9 (16-87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e13.5 (12-65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e58 (14-53)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003e25-OH-vitamin D, nmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003e1,25 dihydroxy vitamin D, pmol/L (normal range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e40.9 (20-79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e45.6 (47.8-190.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e49.9 (37-158)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 775px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUrine metabolic markers\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eCalcium, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e1.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003ePhosphate, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e14.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e258.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eCreatinine, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e89.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eTRP %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e77.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e37.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eTMP/GFR mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e0.94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e1.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 775px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBurosumab therapy\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eAge at initiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e7 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e7 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eDose at initiation, mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e10 (1.3 mg/kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e10 (1.6 mg/kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e10 (0.9 mg/kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eMaximal dose, mg\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e30 (2 mg/kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e30 (4.4 mg/kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e30 (2.5 mg/kg)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eWeight, kg\u003c/p\u003e\n \u003cp\u003e%, z score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e7.445\u003c/p\u003e\n \u003cp\u003e67 (0.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e6.130\u003c/p\u003e\n \u003cp\u003e3 (-1.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e10.800\u003c/p\u003e\n \u003cp\u003e100 (+2.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eLength, cm\u003c/p\u003e\n \u003cp\u003e%, z score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e65.6\u003c/p\u003e\n \u003cp\u003e65 (0.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e60.7\u003c/p\u003e\n \u003cp\u003e0 (-2.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003cp\u003e82 (+0.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eWeight-to-length\u003c/p\u003e\n \u003cp\u003e%, z score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e63 (0.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e56 (0.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e100 (+3.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 775px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSerum metabolic markers\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eCalcium, mg/dL (range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e9.4 (7.4-11.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e10.2 (8.5-10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e10.3 (8.5-10.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003ePhosphate, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e3.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e2.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e2.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eCreatinine, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eAlkaline phosphatase, U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e536 (124-341)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e647 (121.7-472.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e474 (137-535)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003ePTH, pg/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e36.6 (6.7-38.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e27.3 (12-65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e83 (14-53)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003e25-OH-vitamin D, nmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e127\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003e1,25 dihydroxy vitamin D, pmol/L (normal range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e63.4 (20-79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003e45.6 (48-240)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e135 (37-158)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 775px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUrine metabolic markers\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eCalcium, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1.81\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e2.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003ePhosphate, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e31.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e4.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e41.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eCreatinine, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e8.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e59.3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eTRP %\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e86.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e89.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e88\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eTMP/GFR mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e2.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e2.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 340px;\"\u003e\n \u003cp\u003eRenal ultrasound\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003eNormal at 5 yrs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003eNormal at 3 yrs 9 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003eNormal at 1 yr\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 340px;\"\u003e\n \u003cp\u003eDental morbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eComplete primary dentition with an open bite and deep grooves on molars\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 151px;\"\u003e\n \u003cp\u003eNo complications\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eNo complications\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eiFGF23, intact fibroblast growth factor 23; iPTH, intact parathyroid hormone; TRP, total reabsorption of phosphate; TmP/GFR, tubular maximum transport of phosphate to the glomerular filtration rate\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3.\u003c/strong\u003e Skeletal health and alignment: Rickets Severity Score and mechanical axis deviation in XLH patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"699\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 1\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e5 yr 2 mo ♀\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 2\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e4 year 3 mo ♀\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 154px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient 3\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e1 yr 10 mo ♀\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eDuration of burosumab treatment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e4 yrs and 7 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e3 yrs 3 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e1 yr 3 mo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eRSS at last assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 236px;\"\u003e\n \u003cp\u003eMechanical axis deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003eRt 0, Lt 0,\u0026nbsp;\u003cbr\u003e\u0026nbsp;Zone neutral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003eRt 0, Lt 0,\u0026nbsp;\u003cbr\u003e\u0026nbsp;Zone neutral\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 154px;\"\u003e\n \u003cp\u003enot relevant\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"X-linked hypophosphatemic rickets, XLH, burosumab, infants, linear growth, rickets score, phosphate levels, skeletal health","lastPublishedDoi":"10.21203/rs.3.rs-6385587/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6385587/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e X-linked hypophosphatemic rickets (XLH) is a rare inherited metabolic bone disorder caused by excess fibroblast growth factor 23 (FGF23), leading to hypophosphatemia and rickets. Burosumab, a human monoclonal antibody targeting FGF23, was approved for the treatment of XLH in April 2018. By 2022, the FDA extended its approval to include children as young as six months of age.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003e To describe three infants with XLH who began burosumab therapy before one year of age and were monitored for at least one year.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDesign:\u003c/strong\u003e Case series.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Clinical outcomes, including anthropometric measures, skeletal outcomes (Rickets Severity Score [RSS], mechanical axis deviation [MAD], and neck-shaft angle [NSA]), and laboratory parameters, were assessed in a real-world setting.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Two patients demonstrated satisfactory linear growth, and one experienced growth faltering, possibly due to sleep-disordered breathing or phosphate imbalance. These patients received higher doses of burosumab than the current guideline recommendations for achieving treatment goals aimed at normalizing phosphate levels. The patient’s phosphate levels improved but did not normalize. Bone pain was not formally assessed, but parents reported improvements in their children’s conditions. Importantly, two patients with assessable mechanical axes demonstrated neutral mechanical axis deviations, indicating improved lower limb alignment and supporting the therapeutic efficacy of burosumab. All three patients had favorable RSS outcomes, and none developed long bone diaphyseal bowing or coxa vara following this early initiation of burosumab treatment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This case series demonstrated potential benefits of early initiation of burosumab treatment for XLH by showing improvements in growth, phosphate levels, and skeletal outcomes. Burosumab appears well tolerated in infancy, but further research is needed to refine dosing strategies and assess its long-term safety and therapeutic efficacy in young patients with XLH. Meticulous monitoring and individualized care are essential throughout treatment.\u003c/p\u003e","manuscriptTitle":"Burosumab in infants with X-linked hypophosphatemic rickets: a case series","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-07 06:18:33","doi":"10.21203/rs.3.rs-6385587/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2025-05-15T02:07:56+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-04-26T06:17:32+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-25T14:26:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-08T13:25:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"Orphanet Journal of Rare Diseases","date":"2025-04-06T04:23:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"orphanet-journal-of-rare-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ojrd","sideBox":"Learn more about [Orphanet Journal of Rare Diseases](http://ojrd.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ojrd/default.aspx","title":"Orphanet Journal of Rare Diseases","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"01c617ca-c4d8-4601-a2db-79d3c6c93278","owner":[],"postedDate":"May 7th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-01-12T16:08:21+00:00","versionOfRecord":{"articleIdentity":"rs-6385587","link":"https://doi.org/10.1186/s13023-025-04177-2","journal":{"identity":"orphanet-journal-of-rare-diseases","isVorOnly":false,"title":"Orphanet Journal of Rare Diseases"},"publishedOn":"2026-01-08 15:57:00","publishedOnDateReadable":"January 8th, 2026"},"versionCreatedAt":"2025-05-07 06:18:33","video":"","vorDoi":"10.1186/s13023-025-04177-2","vorDoiUrl":"https://doi.org/10.1186/s13023-025-04177-2","workflowStages":[]},"version":"v1","identity":"rs-6385587","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6385587","identity":"rs-6385587","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}