A STUDENT PERSPECTIVE: NEWBORN SCREENING FOR INBORN ERROR OF METABOLISM- CASE STUDY OF METHYLMALONIC ACIDURIA (MMA) USING URINARY GCMS ANALYSIS

Abstract

Methylmalonic acidemia (MMA) is a rare autosomal recessive inborn error of metabolism (IEM) caused by defects in Methylmalonyl-CoA mutase activity or cobalamin (Vitamin B12) metabolism, leading to the accumulation of toxic organic acids, mainly increased MMA in blood & urine. Early diagnosis is critical as untreated MMA can result in severe metabolic decompensation, brain damage and death of the baby. This study is aimed to evaluate the incidence, biochemical profile, and diagnostic significance of MMA by metabolic profiling using urinary Gas Chromatography Mass Spectrometry (GCMS) analysis in a retrospective cohort. A retrospective observational analysis was conducted on 586 suspected cases referred for metabolic evaluation in Jan Dec, 2025. Urinary GCMS analysis data, along with clinical records, were assessed to identify metabolic abnormalities. Among the total 586 cases, 34 (5.80%) showed biochemical evidence of MMA, including 5 mass spectrum confirmed cases (0.85%) and 29 possible MMA cases (4.94%) based on the presence of urinary abnormal biomarkers. Elevated urinary Methylmalonic acid, Methylcitrate, and 3-Hydroxybutyrate were key diagnostic markers, with characteristic total ion chromatogram (TIC) patterns supporting disease identification. The findings highlight MMA as a significant organic acidemia within suspected inborn errors of metabolism and emphasize its variable presentation across different age groups. The study reinforces the importance of expanded newborn screening and confirms urinary GCMS as a reliable gold-standard technique for definitive diagnosis, recommending to include MMA in newborn screening panel. Early detection and timely intervention can thus, be achieved for improving survival and neurodevelopmental outcomes in the affected patients