Newborn screening for methylmalonic acidemia: insights from a retrospective analysis in Hefei, China

Methylmalonic acidemia (MMA) is an autosomal recessive inheritedcongenital metabolic enzyme deficiency disorder that can lead to multi-systemdamage, including the nervous, hematopoietic, hepatic, and renal systems, causingsevere symptoms in the neonatal period and long-term nutritional issues. The detection rate of MMA exhibits significant regional variations. This study aims to find out the incidence rate, biochemical and molecular characteristics, and follow-up status in the Hefei Neonatal Cohort in China. From 2016 to 2023, 34 MMA cases were confirmed biochemically and genetically, comprising 25 combined-type (73.5%) and 9 isolated-type (26.5%) presentations. MMACHC mutations predominated (68.8%), with c.609G>A accounting for 45.5% of variants. Longitudinal surveillance of 26 MMA patients revealed significant morbidity, with 3 cases (11.5%) succumbing to disease complications during follow-up. Comprehensive assessments identified nutritional deficits in 6 patients (23.1%) and neurodevelopmental delays in 4 cases (15.4%), highlighting the multisystemic nature of MMA progression. This study provides a comprehensive characterization of the epidemiological, genetic, and clinical profiles of MMA in the Hefei neonatal cohort. Our results confirm a substantial burden of MMA in this Chinese population. The high morbidity and mortality observed, alongside significant nutritional and neurodevelopmental complications, underscore the multisystemic impact of MMA and highlight the critical need for early diagnosis, sustained follow-up, and genotype-tailored management strategies to improve long-term outcomes.