Neurological Presentations in Pediatric Patients with Inborn Errors of Metabolism: A single-center study

Neurological Presentations in Pediatric Patients with Inborn Errors of Metabolism: A single-center study | 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 Neurological Presentations in Pediatric Patients with Inborn Errors of Metabolism: A single-center study Zahraa Abdelmoneim, Mohamed Abdelghafar Hussein, Heba Eltaher This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5263731/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Inborn errors of metabolism (IEMs) represent a diverse group of genetic disorders characterized by enzyme deficiencies in metabolic pathways, with a collective incidence exceeding 1 in 1,000 live births. Although many patients may appear asymptomatic at birth, they often present with nonspecific neurological symptoms later, complicating diagnosis and treatment. This study aims to identify various neurological manifestations in pediatric patients with IEMs and emphasize the importance of early recognition and management for improved outcomes. Methods This single-center study recruited pediatric patients (ages 0–18) diagnosed with IEMs presenting with neurological symptoms from the Mansoura University Children’s Hospital. Clinical data were collected, including demographic information, seizure characteristics, perinatal events, and family history. Laboratory investigations encompassed metabolic panels, tandem mass spectrometry, and urine organic acid analysis. Neuroimaging, including MRI and EEG, was also performed. Descriptive statistics were used to summarize the prevalence and types of neurological presentations in different IEM disorders. Results The study included 31 patients (15 males, 16 females), predominantly from consanguineous backgrounds (83.9%). The most common diagnosis was organic acidemia (51.6%), followed by mitochondrial disorders (22.6%). Seizures were the most frequent neurological presentation (71%), with generalized tonic-clonic seizures being the most prevalent type. EEG findings varied, with generalized epileptogenic dysfunction observed in 22.6% of cases. MRI results showed white matter involvement in 54.8% of patients, with basal ganglia and thalamic changes noted in organic acidemia cases. Conclusion Neurological manifestations of IEMs are varied, with seizures being a common feature. The study highlights the challenges in diagnosing IEMs due to their rarity and the necessity of a high index of suspicion, particularly in patients with acute encephalopathy. Timely diagnosis and intervention are crucial to prevent irreversible neurological damage. This study underscores the need for further research into IEMs in pediatric populations to enhance clinical understanding and management strategies. Inborn error of metabolism neurological symptoms seizures encephalopathy Background Inborn errors of metabolism (IEMs) encompass a broad range of genetic disorders caused by the deficiency of a specific enzyme in a metabolic pathway [ 1 ]. Though each disorder is rare on its own, IEMs are collectively more prevalent, with a combined incidence of more than 1 in 1,000 live births [ 2 ]. Most IEMs follow an autosomal recessive inheritance pattern. The clinical presentation of IEMs varies widely, from children who appear physically normal to those with distinctive dysmorphic features. While many affected individuals show no symptoms at birth, they may later present with non-specific signs that resemble other serious medical conditions [ 3 ]. In neonates, typical signs of IEMs include reduced consciousness, seizures, and abnormal muscle tone, such as hypo- or hypertonia. Certain metabolic intoxication disorders, such as urea cycle defects (UCD) and organic acidemias (OA), can result in neonatal coma, and early treatment can be crucial. However, when hypotonia is the only symptom, it may indicate IEMs that are rarely treatable [ 4 ]. We aim to outline different neurological presentations in pediatric patients with IEM disorders and various diagnostic modalities with early recognition and management for favorable outcomes. Methodology *Study Population and Recruitment Criteria* Pediatric patients (age range: 0–18 years) diagnosed with inborn errors of metabolism (IEM) and presenting with neurological symptoms were recruited from specialized metabolic clinics at the Mansoura University Children’s Hospital (MUCH). Exclusion criteria included children with neurological presentations caused by acquired metabolic etiologies, such as electrolyte imbalances, hypocalcemia, hypomagnesemia, renal failure, or hypoglycemia not associated with IEM conditions. *Data Collection* Clinical data were collected, including demographic information such as the child’s age, gender, parental consanguinity, and age of seizure onset. Additional data included seizure frequency, perinatal events, developmental milestones, and family history of similar illnesses. A comprehensive clinical examination was performed to identify neurocutaneous markers, discolored hair, alopecia, seborrheic dermatitis, dysmorphic features, microcephaly/macrocephaly, organomegaly, and focal neurological deficits. Laboratory investigations included blood glucose, serum electrolytes, calcium, ammonia, lactate, urine ketones, arterial blood gases, tandem mass spectrometry (TMS), and urine organic acid analysis. Radiological investigations included brain magnetic resonance imaging (MRI) and electroencephalogram (EEG). In addition, special investigations were conducted, including cerebrospinal fluid (CSF) analysis with concurrent blood glucose, CSF lactate, serum glycine, CSF glycine, serum biotinidase levels, urine sulfites, and plasma very long-chain fatty acid assay. Descriptive statistics were used to summarize the prevalence and types of neurological presentations, EEG and MRI findings in different IEM disorders. Results We studied 31 patients 15 males and 16 females, most of them showed positive consanguinity (26 cases) but only 13 cases have positive family history. The age of the study population was (1months-11 years) and CNS presentation was at the age of (7days-6.6 years) as shown in Table 1 . Table 1 Demographics of the Study Population Consanguinity +ve consanguinity 26(83.9%) -ve consanguinity 5(16.1) Gender male 15(48.4) female 16(51.6) Family History +ve family history 13(41.9) -ve family history 18(58.1) Age of study population Median(min-max) 2years( 1months-11 years) Age of CNS presentation Median( min-max) 6 months(7days-6.6 years) The data presented in Table 2 illustrates the frequency and percentage of various diagnoses within a sample population. The predominant diagnosis is Organic acidemia, accounting for 51.6% of the cases, followed by mitochondrial disorders at 22.6%. Urea Cycle Defects and aminoacidopathy represent smaller proportions at 6.5% and 16.1%, respectively. Peroxisomal disorders are the least frequent, comprising only 3.2% of the total. Table 2 Distribution of IEM Diagnosis in the Sample Population number of cases Percent % Valid ORGANIC ACIDEMIA 16 51.6 UREA CYCLE DEFECT 2 6.5 MITOCONDRIAL 7 22.6 AMINOACIDOAPTHY 5 16.1 PERIXOSOMAL 1 3.2 Total 31 100.0 As shown in Tables 3 & 4 , fits were the most common presentation in IEM patients followed by neurodevelopmental delay where dystonia and encephalopathy were the least frequent presentations. Table 3 Spectrum of Central Nervous System (CNS) Presentations in the Sample Population Frequency Percent % Valid ENCEPHALOPATHY 2 6.5 FITS 22 71.0 DYSTONIA 4 12.9 NEURODEVELOPMENTAL DELAY 20 64.5 Table 4 CNS presentations in various types of IEM Encephalopathy Fits Dystonia Neurodevelopmental delay Organic acidemia 1 10 4 5 Urea cycle defect 0 2 0 2 Mitochondrial 1 4 0 7 Aminoacidoapthy 0 5 0 5 Perixosomal 0 1 0 1 Total 2 22 4 20 Tables 5 & 6 show that generalized tonic-clonic fits were the most common type of fits followed by tonic fits and infantile spasm. Both atonic fits and absence seizures were the least frequent fits occurred. Table 5 Type of fits in patients presented with seizures Frequency Percent % Valid Tonic fits 3 9.7 Infantile spasm 2 6.5 Genralized tonic colonic fits 15 48.4 Atonic fits 1 3.2 Abscence seizure 1 3.2 Total 22 100.0 Table 6 type of fits in different types of IEM Tonic fits Infantile spasm Genralized tonic colonic fits Atonic fits Abscence seizure Total Organic acidemia 2 2 6 0 0 10 Urea cycle defect 0 0 2 0 0 2 Mitocondrial 0 0 4 0 0 4 Aminoacidoapthy 0 0 3 1 1 5 Perixosomal 1 0 0 0 0 1 Total 3 2 15 1 1 22 Table 7 shows that 68% of metabolic seizures occurred in infancy, 27.2% occurred in the neonatal period and only one case occurred beyond infancy. Table 7 Age Distribution of Metabolic Seizures Median (Minimum-maximum) 6 months(8 days- 42 months) Number of cases presented with seizures in neonatal life(< 28 days) 6 cases(27.2%) Number of cases presented with seizures from neonatal period till end of infancy period( 28days − 24 months) 15 cases(68%) Number of cases presented with seizures beyond infancy till 5 years 1 case(0.05%) Number of cases 22 cases Table 8 EEG Findings in the Sample Population Frequency Percent Valid Percent Cumulative Percent Normal 8 25.8 25.8 25.8 focal with bilateral discharge 2 6.5 6.5 32.3 centortemporal epileptiform discharge wit focal epileptiorm discharge 2 6.5 6.5 38.7 generalized epileptogenic dysfunction 7 22.6 22.6 61.3 mild focal frontal activity 3 9.7 9.7 71.0 generalized seizures suggesting Lennox Gastaut 5 16.1 16.1 87.1 epileptogenic irritation in centeroencephalic area 3 9.7 9.7 96.8 modified hypsarrhthmia 1 3.2 3.2 100.0 Total 31 100.0 100.0 Tables 9 & 10 show that white matter affection was the commonest area affected followed by the Basal gangalia and thalasmus. Only one case had stroke. Four cases had normal MRI brain Table 9 MRI Findings in the Sample Population Frequency Percent Valid Basal gangalia and thalasmus 9 29.0 White matter 17 54.8 Stroke 1 3.2 Normal 4 12.9 Total 31 100.0 Table 10 MRI Findings among Cases with Inborn Errors of Metabolism Basal gangalia and thalasmus White matter Stroke Normal Total Organic acidemia 7 7 1 1 16 Urea cycle defect 0 2 0 0 2 Mitocondrial 2 3 0 2 7 Aminoacidoapthy 0 4 0 1 5 Perixosomal 0 1 0 0 1 Total 9 17 1 4 31 Discussion Neurometabolic diseases are a broad subset of inborn errors of metabolism (IEMs) that specifically impact the brain and remain incompletely characterized. These disorders arise from genetic defects that disrupt the intermediary metabolism of carbohydrates, lipids, amino acids, vitamins, or energy production pathways [ 4 ] . Over 200 different metabolic disorders are known to cause seizures. In these conditions, epilepsy may either be the primary presenting symptom or part of a broader set of neurological and metabolic manifestations within a complex phenotype [ 5 ]. We studied various neurological presentations, radiological imaging and EEG findings in 31 pediatric patients diagnosed with different IEM disorders. Organic academia was the most common disorder in 16 cases representing 51.5% of the cases while UCD, mitochondrial, aminoacidopathies and perixosomal were the rest of cases. The age of our study population ranges from 1months to11 years which means that for some of these children with metabolic diseases, irreversible sequelae were already established as the age of CNS presentation ranged from 7days-6.6 years. There was no sex selection as most of IEM disorders are inherited in an autosomal recessive pattern. Our patients presented with different neurological presentations with seizures being the most common presentation in 71% of cases, neurodevelopmental delay was in 64.5%, dystonia was in 12.9% of cases, and encephalopathy and coma was in 6.5% of cases. Though IEM are a relatively infrequent cause of epilepsy, epileptic seizures are a common feature in several IEM. Epilepsies associated with IEM share certain features [ 6 ]. An early age of presentation, co-morbid developmental delay/regression, and resistance to conventional antiepileptic drug therapy are common to many of these disorders [ 7 ] and this is consistent with our findings that seizure were the most common presentation in 71% of the cases associated with developmental delay and non-responsiveness to several antiepileptic drugs . We reported different types of seizures in 22 of our patients, generalized tonic clonic fits were in 15 of our cases, tonic seizures were in 3 cases, infantile spasm in two cases while atonic fits and absence seizures each one in one case . Neonatal seizures were reported in 6 cases out of 22 cases presented with seizures while 15 cases were presented beyond neonatal period till infancy and only one case presented before 5 years old. Loman et al. in their study found that IEMs caused neonatal seizures in 5/221 (2,3%) of newborns [ 8 ]. Reversely, epileptic seizures are a common feature in several IEMs; indeed, 85% of IEMs display predominantly neurological manifestations [ 9 ]. In our study we didn’t report significant association between type of seizures and the type of IEM as generalized tonic clonic fits were presented in organic academia, amnioacidopathy, mitochondrial and urea cycle defect. There were different EEG pattern in our study with no specific associations with certain IEM disorder. Electroencephalographic (EEG) findings in infants with epileptic encephalopathies typically change as the child’s brain matures [ 10 ]. For example, a burst-suppression pattern may be seen during the neonatal period, hypsarrhythmia may appear in infancy, and the EEG may evolve into multifocal or generalized slow spike-wave discharges in early childhood [ 11 ]. Additionally, epilepsy resulting from an inborn error of metabolism (IEM) often presents with variable clinical and EEG features, making it challenging to classify as a specific epileptic syndrome[ 12 ]. Metabolic disorders are just one of the many causes of acute encephalopathy, and establishing a diagnosis can be challenging in the early stages. However, early diagnosis and timely treatment are crucial, as there is a limited window to prevent irreversible brain damage. Acute encephalopathy is a frequent and potentially life-threatening medical emergency in patients with inborn errors of metabolism (IEM) [ 13 ]. In our study, two cases only were presented with acute encephalopathy and coma. Precise suspicion, early diagnosis and treatment favor the outcome of these patients. The difference in clinical findings is because, in the present study, the sample consisted of outpatients, while those in the cited literature were from pediatric or neonatal intensive care units. Neuroimaging is essential for diagnosing and monitoring treatment [ 14 ]. The neuroimaging findings can differ both within and among inborn errors of metabolism (IEMs), presenting a spectrum from normal brain imaging to diffuse, severe central nervous system disease. This variability is influenced by several factors, including the type and severity of the metabolic pathway defect, the extent of toxic byproduct accumulation (if applicable), the brain's maturity at the time of the insult, the duration of the injury, compensatory mechanisms, and the timing of the imaging during the course of the disease [ 15 ]. Some patterns of characteristic brain involvement have been described: amino acid disorders (i.e., maple syrup urine disease) predominantly involve white matter tracts; organic acid disorders usually involve deep gray matter; energy production/lactic acidosis disorders may involve both deep grey and white matter [ 16 ]. In our study 4 cases of aminoacidopathies showed radiological finings involving white matter; 7 cases of organic acidemias affecting gray matter mainly thalamus and basal ganglia while 7 cases affecting white matter. However, these patterns of involvement are nonspecific and may sometimes overlap with each other. Strength and limitations: Few cases due to the rarity of the disease, also it needs high level of suspicion to diagnose especially in the absence of the screening to asymptomatic neonates. But our study is one of the first studies which highlighted various patterns of presentations and findings in IEM in neonatal and pediatric age groups. Also it highlights the importance of including IEM cases in clinical discussions and emphasizes that IEM should not be considered a diagnosis of exclusion, but rather a potential diagnosis from the outset of the investigation. Further research with a larger sample size and inclusion of hospital-based cases is needed to better determine the prevalence of IEM. Conclusion Many of IEM are amenable to specific treatments and hence timely and appropriate diagnosis is essential to prevent irreversible brain damage .This requires knowledge about the clinical presentation, standardized vitamin trials, and availability of biochemical tests for diagnosis. IEMs that remain undiagnosed by clinical and biochemical testing, next-generation sequencing with gene panels, and whole exome sequencing may increase the diagnostic yield. Abbreviations CNS central nervous system CSF cerebrospinal fluid EEG electroencephalogram IEMs inborn errors of metabolism MRI magnetic resonance imaging MUCH Mansoura University Children's Hospital OA organic acidemia TMS tandem mass spectrometry UCD urea cycle defect Declarations Ethics approval and consent to participate Informed consent was obtained from parents and Institutional Review Board, Mansoura Faculty of Medicine, Mansoura University approved the study, Code Number: “R.24.02.2514” Consent for publication Not applicable Availability of data and materials The datasets during and/or analysed during the current study available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding No funding Authors' contributions ZA helped in the study design, collecting data, and revising of the final manuscript. MH helped with statistical analysis and data analysis. HE helped formulate the research question, the study design and writing. All authors have substantially contributed intellectually to the study and approved the final manuscript. Acknowledgment We would like to extend our deepest gratitude to the patients and their parents, whose courage, resilience, and unwavering commitment have been invaluable to this research. Your participation and willingness to share your experiences have significantly contributed to our understanding of neurological presentation of different inborn error of metabolism. We are profoundly grateful for your trust and cooperation, which have been instrumental in advancing this important work. Thank you for your strength and dedication. References El-Hattab AW. Inborn errors of metabolism. Clin Perinatol. 2015;42(2):413–39. Campeau PM, Scriver CR, Mitchell JJ. A 25-year longitudinal analysis of treatment efficacy in inborn errors of metabolism. Mol Genet Metab. 2008;95(1–2):11–6. Kolker S, et al. Erratum to: The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation. J Inherit Metab Dis. 2015;38(6):1155–6. Saudubray JM, Garcia-Cazorla A. Inborn Errors of Metabolism Overview: Pathophysiology, Manifestations, Evaluation, and Management. Pediatr Clin North Am. 2018;65(2):179–208. Rahman S, et al. Inborn errors of metabolism causing epilepsy. Dev Med Child Neurol. 2013;55(1):23–36. Prasad AN, Hoffmann GF. Early onset epilepsy and inherited metabolic disorders: diagnosis and management. Can J Neurol Sci. 2010;37(3):350–8. Mercimek-Mahmutoglu S, et al. Diagnostic yield of genetic testing in epileptic encephalopathy in childhood. Epilepsia. 2015;56(5):707–16. Loman AM, et al. Neonatal seizures: aetiology by means of a standardized work-up. Eur J Paediatr Neurol. 2014;18(3):360–7. Choudhry S, et al. Etiology and outcome of inborn errors of metabolism. J Pak Med Assoc. 2013;63(9):1112–6. Campistol J, Plecko B. Treatable newborn and infant seizures due to inborn errors of metabolism. Epileptic Disord. 2015;17(3):229–42. Jain P, Sharma S, Tripathi M. Diagnosis and management of epileptic encephalopathies in children. Epilepsy Res Treat. 2013;2013:501981. Sharma S, Prasad AN. Genetic testing of epileptic encephalopathies of infancy: an approach. Can J Neurol Sci. 2013;40(1):10–6. Leonard JV. Acute metabolic encephalopathy: an introduction. J Inherit Metab Dis. 2005;28(3):403–6. Whitehead MT, Lai LM, Bluml S. Clinical (1)H MRS in childhood neurometabolic diseases - part 2: MRS signatures. Neuroradiology. 2022;64(6):1111–26. Biswas A, et al. Clinico-radiological phenotyping and diagnostic pathways in childhood neurometabolic disorders-a practical introductory guide. Transl Pediatr. 2021;10(4):1201–30. Yoon HJ, et al. Devastating metabolic brain disorders of newborns and young infants. Radiographics. 2014;34(5):1257–72. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 05 Sep, 2025 Reviewers agreed at journal 29 May, 2025 Reviewers invited by journal 29 Oct, 2024 Editor assigned by journal 22 Oct, 2024 First submitted to journal 21 Oct, 2024 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5263731","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":371684021,"identity":"68a04da4-a67c-40a0-89d2-0083e6b84a1e","order_by":0,"name":"Zahraa Abdelmoneim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4UlEQVRIiWNgGAWjYBACAwYGNhAtx8bMfABIS8gQrcWYj50tAaSFh2gtifP4eQxADMJazPkPP3tcUWPH2MbM8/nVjRoLHgb2w0c34NNi2XDM3PDMsWRmNmbebdY5x4AO40lLu4HXYQcbzCQb2JjZQFqMc9iAWiR4zPBrOcz+TbLhXz0PGzPPM+Ocf8RoOcZjJtnYdlgCqIX5cW4bMVrO8JRJNvYdNwC6zYw5t0+Ch42gX84f3ybZ8K26fn7/4cefc77VyfGzHz6GVwsyYJMAk8QqBwHmD6SoHgWjYBSMgpEDANTCPsKJn59NAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0009-0005-3632-6410","institution":"Mansoura University Children's Hospital","correspondingAuthor":true,"prefix":"","firstName":"Zahraa","middleName":"","lastName":"Abdelmoneim","suffix":""},{"id":371684022,"identity":"0d1a5206-70d3-4ee3-9c55-94e67280f5f1","order_by":1,"name":"Mohamed Abdelghafar Hussein","email":"","orcid":"","institution":"Kafrelsheikh University","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"Abdelghafar","lastName":"Hussein","suffix":""},{"id":371684023,"identity":"a086a0b3-a012-4e6f-a2e4-e10c79e43f5c","order_by":2,"name":"Heba Eltaher","email":"","orcid":"","institution":"Mansoura University Children's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Heba","middleName":"","lastName":"Eltaher","suffix":""}],"badges":[],"createdAt":"2024-10-14 21:55:35","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5263731/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5263731/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":68515637,"identity":"6d829f03-81ef-486e-9ab3-52d65b6e8f33","added_by":"auto","created_at":"2024-11-08 06:51:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":516293,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5263731/v1/a02afc7e-4cca-4077-932e-f03dab21920c.pdf"}],"financialInterests":"","formattedTitle":"Neurological Presentations in Pediatric Patients with Inborn Errors of Metabolism: A single-center study","fulltext":[{"header":"Background","content":"\u003cp\u003eInborn errors of metabolism (IEMs) encompass a broad range of genetic disorders caused by the deficiency of a specific enzyme in a metabolic pathway [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Though each disorder is rare on its own, IEMs are collectively more prevalent, with a combined incidence of more than 1 in 1,000 live births [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Most IEMs follow an autosomal recessive inheritance pattern. The clinical presentation of IEMs varies widely, from children who appear physically normal to those with distinctive dysmorphic features. While many affected individuals show no symptoms at birth, they may later present with non-specific signs that resemble other serious medical conditions [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In neonates, typical signs of IEMs include reduced consciousness, seizures, and abnormal muscle tone, such as hypo- or hypertonia. Certain metabolic intoxication disorders, such as urea cycle defects (UCD) and organic acidemias (OA), can result in neonatal coma, and early treatment can be crucial. However, when hypotonia is the only symptom, it may indicate IEMs that are rarely treatable [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe aim to outline different neurological presentations in pediatric patients with IEM disorders and various diagnostic modalities with early recognition and management for favorable outcomes.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cp\u003e*Study Population and Recruitment Criteria*\u003c/p\u003e \u003cp\u003ePediatric patients (age range: 0\u0026ndash;18 years) diagnosed with inborn errors of metabolism (IEM) and presenting with neurological symptoms were recruited from specialized metabolic clinics at the Mansoura University Children\u0026rsquo;s Hospital (MUCH). Exclusion criteria included children with neurological presentations caused by acquired metabolic etiologies, such as electrolyte imbalances, hypocalcemia, hypomagnesemia, renal failure, or hypoglycemia not associated with IEM conditions.\u003c/p\u003e \u003cp\u003e*Data Collection*\u003c/p\u003e \u003cp\u003eClinical data were collected, including demographic information such as the child\u0026rsquo;s age, gender, parental consanguinity, and age of seizure onset. Additional data included seizure frequency, perinatal events, developmental milestones, and family history of similar illnesses. A comprehensive clinical examination was performed to identify neurocutaneous markers, discolored hair, alopecia, seborrheic dermatitis, dysmorphic features, microcephaly/macrocephaly, organomegaly, and focal neurological deficits.\u003c/p\u003e \u003cp\u003eLaboratory investigations included blood glucose, serum electrolytes, calcium, ammonia, lactate, urine ketones, arterial blood gases, tandem mass spectrometry (TMS), and urine organic acid analysis. Radiological investigations included brain magnetic resonance imaging (MRI) and electroencephalogram (EEG).\u003c/p\u003e \u003cp\u003eIn addition, special investigations were conducted, including cerebrospinal fluid (CSF) analysis with concurrent blood glucose, CSF lactate, serum glycine, CSF glycine, serum biotinidase levels, urine sulfites, and plasma very long-chain fatty acid assay.\u003c/p\u003e \u003cp\u003eDescriptive statistics were used to summarize the prevalence and types of neurological presentations, EEG and MRI findings in different IEM disorders.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eWe studied 31 patients 15 males and 16 females, most of them showed positive consanguinity (26 cases) but only 13 cases have positive family history. The age of the study population was (1months-11 years) and CNS presentation was at the age of (7days-6.6 years) as shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographics of the Study Population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eConsanguinity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e+ve consanguinity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26(83.9%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-ve consanguinity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(16.1)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003emale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(48.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003efemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16(51.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eFamily History\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e+ve family history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13(41.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-ve family history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18(58.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge of study population\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian(min-max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2years( 1months-11 years)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge of CNS presentation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMedian( min-max)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 months(7days-6.6 years)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe data presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e illustrates the frequency and percentage of various diagnoses within a sample population. The predominant diagnosis is Organic acidemia, accounting for 51.6% of the cases, followed by mitochondrial disorders at 22.6%. Urea Cycle Defects and aminoacidopathy represent smaller proportions at 6.5% and 16.1%, respectively. Peroxisomal disorders are the least frequent, comprising only 3.2% of the total.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDistribution of IEM Diagnosis in the Sample Population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003enumber of cases\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercent %\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eValid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eORGANIC ACIDEMIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e51.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUREA CYCLE DEFECT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMITOCONDRIAL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAMINOACIDOAPTHY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e16.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePERIXOSOMAL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAs shown in Tables \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u0026amp; \u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, fits were the most common presentation in IEM patients followed by neurodevelopmental delay where dystonia and encephalopathy were the least frequent presentations.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSpectrum of Central Nervous System (CNS) Presentations in the Sample Population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercent %\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003eValid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eENCEPHALOPATHY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFITS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e71.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDYSTONIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNEURODEVELOPMENTAL DELAY\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e64.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCNS presentations in various types of IEM\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eEncephalopathy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFits\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDystonia\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNeurodevelopmental delay\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOrganic acidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrea cycle defect\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMitochondrial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAminoacidoapthy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePerixosomal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTables\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u0026amp; \u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e show that generalized tonic-clonic fits were the most common type of fits followed by tonic fits and infantile spasm. Both atonic fits and absence seizures were the least frequent fits occurred.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eType of fits in patients presented with seizures\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercent %\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003eValid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTonic fits\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eInfantile spasm\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGenralized tonic colonic fits\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAtonic fits\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbscence seizure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003etype of fits in different types of IEM\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTonic fits\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eInfantile spasm\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eGenralized tonic colonic fits\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAtonic fits\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAbscence seizure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOrganic acidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrea cycle defect\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMitocondrial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAminoacidoapthy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePerixosomal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e shows that 68% of metabolic seizures occurred in infancy, 27.2% occurred in the neonatal period and only one case occurred beyond infancy.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAge Distribution of Metabolic Seizures\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian (Minimum-maximum)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 months(8 days- 42 months)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of cases presented with seizures in neonatal life(\u0026lt;\u0026thinsp;28 days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 cases(27.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of cases presented with seizures from neonatal period till end of infancy period( 28days \u0026minus;\u0026thinsp;24 months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 cases(68%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of cases presented with seizures beyond infancy till 5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 case(0.05%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of cases\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 cases\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEEG Findings in the Sample Population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePercent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eValid Percent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCumulative Percent\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"1\" nameend=\"c5\" namest=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e25.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003efocal with bilateral discharge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ecentortemporal epileptiform discharge wit focal epileptiorm discharge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003egeneralized epileptogenic dysfunction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e61.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emild focal frontal activity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e71.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003egeneralized seizures suggesting Lennox Gastaut\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e87.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eepileptogenic irritation in centeroencephalic area\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e96.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emodified hypsarrhthmia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTables\u0026nbsp;\u003cspan refid=\"Tab9\" class=\"InternalRef\"\u003e9\u003c/span\u003e\u0026amp; \u003cspan refid=\"Tab10\" class=\"InternalRef\"\u003e10\u003c/span\u003e show that white matter affection was the commonest area affected followed by the Basal gangalia and thalasmus. Only one case had stroke. Four cases had normal MRI brain\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab9\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 9\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMRI Findings in the Sample Population\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFrequency\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePercent\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003eValid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBasal gangalia and thalasmus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWhite matter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e54.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStroke\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab10\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 10\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMRI Findings among Cases with Inborn Errors of Metabolism\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBasal gangalia and thalasmus\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWhite matter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eStroke\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"4\" rowspan=\"5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOrganic acidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUrea cycle defect\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMitocondrial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAminoacidoapthy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePerixosomal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eNeurometabolic diseases are a broad subset of inborn errors of metabolism (IEMs) that specifically impact the brain and remain incompletely characterized. These disorders arise from genetic defects that disrupt the intermediary metabolism of carbohydrates, lipids, amino acids, vitamins, or energy production pathways [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] .\u003c/p\u003e \u003cp\u003eOver 200 different metabolic disorders are known to cause seizures. In these conditions, epilepsy may either be the primary presenting symptom or part of a broader set of neurological and metabolic manifestations within a complex phenotype [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe studied various neurological presentations, radiological imaging and EEG findings in 31 pediatric patients diagnosed with different IEM disorders. Organic academia was the most common disorder in 16 cases representing 51.5% of the cases while UCD, mitochondrial, aminoacidopathies and perixosomal were the rest of cases.\u003c/p\u003e \u003cp\u003eThe age of our study population ranges from 1months to11 years which means that for some of these children with metabolic diseases, irreversible sequelae were already established as the age of CNS presentation ranged from 7days-6.6 years.\u003c/p\u003e \u003cp\u003eThere was no sex selection as most of IEM disorders are inherited in an autosomal recessive pattern.\u003c/p\u003e \u003cp\u003eOur patients presented with different neurological presentations with seizures being the most common presentation in 71% of cases, neurodevelopmental delay was in 64.5%, dystonia was in 12.9% of cases, and encephalopathy and coma was in 6.5% of cases.\u003c/p\u003e \u003cp\u003eThough IEM are a relatively infrequent cause of epilepsy, epileptic seizures are a common feature in several IEM. Epilepsies associated with IEM share certain features [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. An early age of presentation, co-morbid developmental delay/regression, and resistance to conventional antiepileptic drug therapy are common to many of these disorders [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] and this is consistent with our findings that seizure were the most common presentation in 71% of the cases associated with developmental delay and non-responsiveness to several antiepileptic drugs .\u003c/p\u003e \u003cp\u003eWe reported different types of seizures in 22 of our patients, generalized tonic clonic fits were in 15 of our cases, tonic seizures were in 3 cases, infantile spasm in two cases while atonic fits and absence seizures each one in one case .\u003c/p\u003e \u003cp\u003eNeonatal seizures were reported in 6 cases out of 22 cases presented with seizures while 15 cases were presented beyond neonatal period till infancy and only one case presented before 5 years old. Loman et al. in their study found that IEMs caused neonatal seizures in 5/221 (2,3%) of newborns [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Reversely, epileptic seizures are a common feature in several IEMs; indeed, 85% of IEMs display predominantly neurological manifestations [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study we didn\u0026rsquo;t report significant association between type of seizures and the type of IEM as generalized tonic clonic fits were presented in organic academia, amnioacidopathy, mitochondrial and urea cycle defect.\u003c/p\u003e \u003cp\u003eThere were different EEG pattern in our study with no specific associations with certain IEM disorder. Electroencephalographic (EEG) findings in infants with epileptic encephalopathies typically change as the child\u0026rsquo;s brain matures [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. For example, a burst-suppression pattern may be seen during the neonatal period, hypsarrhythmia may appear in infancy, and the EEG may evolve into multifocal or generalized slow spike-wave discharges in early childhood [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Additionally, epilepsy resulting from an inborn error of metabolism (IEM) often presents with variable clinical and EEG features, making it challenging to classify as a specific epileptic syndrome[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMetabolic disorders are just one of the many causes of acute encephalopathy, and establishing a diagnosis can be challenging in the early stages. However, early diagnosis and timely treatment are crucial, as there is a limited window to prevent irreversible brain damage. Acute encephalopathy is a frequent and potentially life-threatening medical emergency in patients with inborn errors of metabolism (IEM) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn our study, two cases only were presented with acute encephalopathy and coma. Precise suspicion, early diagnosis and treatment favor the outcome of these patients. The difference in clinical findings is because, in the present study, the sample consisted of outpatients, while those in the cited literature were from pediatric or neonatal intensive care units.\u003c/p\u003e \u003cp\u003eNeuroimaging is essential for diagnosing and monitoring treatment [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The neuroimaging findings can differ both within and among inborn errors of metabolism (IEMs), presenting a spectrum from normal brain imaging to diffuse, severe central nervous system disease. This variability is influenced by several factors, including the type and severity of the metabolic pathway defect, the extent of toxic byproduct accumulation (if applicable), the brain's maturity at the time of the insult, the duration of the injury, compensatory mechanisms, and the timing of the imaging during the course of the disease [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSome patterns of characteristic brain involvement have been described: amino acid disorders (i.e., maple syrup urine disease) predominantly involve white matter tracts; organic acid disorders usually involve deep gray matter; energy production/lactic acidosis disorders may involve both deep grey and white matter [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In our study 4 cases of aminoacidopathies showed radiological finings involving white matter; 7 cases of organic acidemias affecting gray matter mainly thalamus and basal ganglia while 7 cases affecting white matter. However, these patterns of involvement are nonspecific and may sometimes overlap with each other.\u003c/p\u003e\n\u003ch3\u003eStrength and limitations:\u003c/h3\u003e\n\u003cp\u003eFew cases due to the rarity of the disease, also it needs high level of suspicion to diagnose especially in the absence of the screening to asymptomatic neonates. But our study is one of the first studies which highlighted various patterns of presentations and findings in IEM in neonatal and pediatric age groups. Also it highlights the importance of including IEM cases in clinical discussions and emphasizes that IEM should not be considered a diagnosis of exclusion, but rather a potential diagnosis from the outset of the investigation. Further research with a larger sample size and inclusion of hospital-based cases is needed to better determine the prevalence of IEM.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eMany of IEM are amenable to specific treatments and hence timely and appropriate diagnosis is essential to prevent irreversible brain damage .This requires knowledge about the clinical presentation, standardized vitamin trials, and availability of biochemical tests for diagnosis. IEMs that remain undiagnosed by clinical and biochemical testing, next-generation sequencing with gene panels, and whole exome sequencing may increase the diagnostic yield.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCNS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecentral nervous system\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCSF\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecerebrospinal fluid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEEG\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eelectroencephalogram\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIEMs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003einborn errors of metabolism\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emagnetic resonance imaging\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMUCH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMansoura University Children's Hospital\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eOA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eorganic acidemia\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTMS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etandem mass spectrometry\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eUCD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eurea cycle defect\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cu\u003eEthics approval and consent to participate\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from parents and Institutional Review Board, Mansoura Faculty of Medicine, Mansoura University approved the study, Code Number: \u0026nbsp;\u0026ldquo;R.24.02.2514\u0026rdquo;\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConsent for publication\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAvailability of data and materials\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets during and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eCompeting interests\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eFunding\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eNo funding\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAuthors\u0026apos; contributions\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eZA helped in the study design, collecting data,\u0026nbsp;and revising of the final manuscript.\u003c/p\u003e\n\u003cp\u003eMH helped with statistical analysis and data analysis.\u003c/p\u003e\n\u003cp\u003eHE helped formulate the research question, the study design and writing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors have substantially contributed intellectually to the study and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eAcknowledgment\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to extend our deepest gratitude to the patients and their parents, whose courage, resilience, and unwavering commitment have been invaluable to this research. Your participation and willingness to share your experiences have significantly contributed to our understanding of neurological presentation of different inborn error of metabolism. We are profoundly grateful for your trust and cooperation, which have been instrumental in advancing this important work. Thank you for your strength and dedication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eEl-Hattab AW. Inborn errors of metabolism. Clin Perinatol. 2015;42(2):413\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCampeau PM, Scriver CR, Mitchell JJ. A 25-year longitudinal analysis of treatment efficacy in inborn errors of metabolism. Mol Genet Metab. 2008;95(1\u0026ndash;2):11\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKolker S, et al. Erratum to: The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 1: the initial presentation. J Inherit Metab Dis. 2015;38(6):1155\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaudubray JM, Garcia-Cazorla A. Inborn Errors of Metabolism Overview: Pathophysiology, Manifestations, Evaluation, and Management. Pediatr Clin North Am. 2018;65(2):179\u0026ndash;208.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRahman S, et al. Inborn errors of metabolism causing epilepsy. Dev Med Child Neurol. 2013;55(1):23\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrasad AN, Hoffmann GF. Early onset epilepsy and inherited metabolic disorders: diagnosis and management. Can J Neurol Sci. 2010;37(3):350\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMercimek-Mahmutoglu S, et al. Diagnostic yield of genetic testing in epileptic encephalopathy in childhood. Epilepsia. 2015;56(5):707\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLoman AM, et al. Neonatal seizures: aetiology by means of a standardized work-up. Eur J Paediatr Neurol. 2014;18(3):360\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoudhry S, et al. Etiology and outcome of inborn errors of metabolism. J Pak Med Assoc. 2013;63(9):1112\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCampistol J, Plecko B. Treatable newborn and infant seizures due to inborn errors of metabolism. Epileptic Disord. 2015;17(3):229\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJain P, Sharma S, Tripathi M. Diagnosis and management of epileptic encephalopathies in children. Epilepsy Res Treat. 2013;2013:501981.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma S, Prasad AN. Genetic testing of epileptic encephalopathies of infancy: an approach. Can J Neurol Sci. 2013;40(1):10\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeonard JV. Acute metabolic encephalopathy: an introduction. J Inherit Metab Dis. 2005;28(3):403\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWhitehead MT, Lai LM, Bluml S. Clinical (1)H MRS in childhood neurometabolic diseases - part 2: MRS signatures. Neuroradiology. 2022;64(6):1111\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBiswas A, et al. Clinico-radiological phenotyping and diagnostic pathways in childhood neurometabolic disorders-a practical introductory guide. Transl Pediatr. 2021;10(4):1201\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYoon HJ, et al. Devastating metabolic brain disorders of newborns and young infants. Radiographics. 2014;34(5):1257\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Inborn error of metabolism, neurological symptoms, seizures, encephalopathy","lastPublishedDoi":"10.21203/rs.3.rs-5263731/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5263731/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eInborn errors of metabolism (IEMs) represent a diverse group of genetic disorders characterized by enzyme deficiencies in metabolic pathways, with a collective incidence exceeding 1 in 1,000 live births. Although many patients may appear asymptomatic at birth, they often present with nonspecific neurological symptoms later, complicating diagnosis and treatment. This study aims to identify various neurological manifestations in pediatric patients with IEMs and emphasize the importance of early recognition and management for improved outcomes.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis single-center study recruited pediatric patients (ages 0\u0026ndash;18) diagnosed with IEMs presenting with neurological symptoms from the Mansoura University Children\u0026rsquo;s Hospital. Clinical data were collected, including demographic information, seizure characteristics, perinatal events, and family history. Laboratory investigations encompassed metabolic panels, tandem mass spectrometry, and urine organic acid analysis. Neuroimaging, including MRI and EEG, was also performed. Descriptive statistics were used to summarize the prevalence and types of neurological presentations in different IEM disorders.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe study included 31 patients (15 males, 16 females), predominantly from consanguineous backgrounds (83.9%). The most common diagnosis was organic acidemia (51.6%), followed by mitochondrial disorders (22.6%). Seizures were the most frequent neurological presentation (71%), with generalized tonic-clonic seizures being the most prevalent type. EEG findings varied, with generalized epileptogenic dysfunction observed in 22.6% of cases. MRI results showed white matter involvement in 54.8% of patients, with basal ganglia and thalamic changes noted in organic acidemia cases.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eNeurological manifestations of IEMs are varied, with seizures being a common feature. The study highlights the challenges in diagnosing IEMs due to their rarity and the necessity of a high index of suspicion, particularly in patients with acute encephalopathy. Timely diagnosis and intervention are crucial to prevent irreversible neurological damage. This study underscores the need for further research into IEMs in pediatric populations to enhance clinical understanding and management strategies.\u003c/p\u003e","manuscriptTitle":"Neurological Presentations in Pediatric Patients with Inborn Errors of Metabolism: A single-center study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-11-08 06:50:54","doi":"10.21203/rs.3.rs-5263731/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2025-09-05T13:39:01+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-05-29T22:58:47+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-10-29T10:18:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-10-22T12:19:01+00:00","index":"","fulltext":""},{"type":"submitted","content":"Italian Journal of Pediatrics","date":"2024-10-21T07:03:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"italian-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"itjp","sideBox":"Learn more about [Italian Journal of Pediatrics](http://ijponline.biomedcentral.com)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ITJP/default.aspx","title":"Italian Journal of Pediatrics","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"54208f30-36d0-48e5-bba8-7862526ad58f","owner":[],"postedDate":"November 8th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-12-26T11:53:13+00:00","versionOfRecord":[],"versionCreatedAt":"2024-11-08 06:50:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5263731","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5263731","identity":"rs-5263731","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}