Medium-chain acyl-CoA dehydrogenase deficiency: A ten-year single-center case series from India.

BACKGROUND: Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common fatty acid oxidation disorder in Caucasians, but remains rare in India. Data on its clinical, biochemical, and genetic profile in the Indian population are limited. METHODS: This single-center study analyzed 21 patients diagnosed with MCADD over ten years. Acylcarnitine profiling was performed using LC-MS/MS and urinary organic acids by GC-MS. Whole exome sequencing was available for 11 patients. Carrier frequency was estimated from 3044 unrelated Indian exomes. RESULTS: Eighteen patients (85.7%) presented within the first year of life. Major manifestations included metabolic acidosis, encephalopathy, and hypoglycemic seizures. Plasma C6, C8, and C10 acylcarnitines and C8/C2, C8/C10 ratios were significantly elevated (p < 0.0001). Encephalopathy correlated with elevated urinary 7-hydroxyoctanoic acid and mortality (p = 0.02). Eight distinct ACADM variants were identified, predominantly homozygous. The European founder variant c.985 A > G was infrequent. Carrier frequency was 1 in 152, with an estimated incidence of 1:370,637 in India. Overall mortality was 19%. CONCLUSION: MCADD is rare but clinically severe in India. Population-specific mutation patterns were observed. In this exploratory case series, the blood C8/C10 acylcarnitine ratio was significantly lower in deceased patients than in survivors (2.80 ± 2.20 vs. 11.28 ± 3.07, p < 0.001), suggesting potential prognostic utility that warrants validation in larger cohorts. Early diagnosis and prompt management significantly improve outcomes.