Clinical and Genetic Spectrum of 50 Children with Inborn Errors of Metabolism from Central India

Area of Science:

• Pediatrics
• Medical Genetics
• Metabolic Disorders

Background:

• Inborn errors of metabolism (IEMs) are a heterogeneous group of genetic disorders.
• Early diagnosis and management are crucial for improving outcomes in affected children.
• Phenotypic variability often complicates the diagnostic process for IEMs.

Purpose of the Study:

• To analyze the spectrum of IEMs in children presenting to a tertiary care center in central India.
• To evaluate the utility of different diagnostic modalities based on predominant clinical phenotypes.
• To identify common IEMs and genetic variations in the studied pediatric population.

Main Methods:

• Retrospective analysis of 50 pediatric patients diagnosed with IEMs.
• Classification of patients based on predominant clinical phenotypes: acute encephalopathy, developmental delay/seizures, neuroregression, or organomegaly.
• Review of diagnostic tests utilized, including acylcarnitine profiles, urine organic acids, exome sequencing, and specific enzyme assays.

Main Results:

• Lysosomal storage disorders were the most frequent (26%), followed by organic acidurias (16%).
• Genetic variations were identified in 50% of the patients.
• Diagnostic yield varied by phenotype: acylcarnitine profiles/urine organic acids (62.5% for acute encephalopathy), exome sequencing (55.5% for neuroregression), and enzyme assays (83.3% for organomegaly).
• Children with developmental delay/seizures required a broader range of investigations.

Conclusions:

• A diverse range of IEMs affects children in central India, with lysosomal storage disorders being predominant.
• Diagnostic test selection should be guided by the presenting clinical phenotype for optimal yield.
• Genetic testing plays a significant role in identifying causative variations in IEMs.