Clinical and genetic analysis of 658 children with repeat hospitalization for methylmalonic aciduria from central China: a single-center retrospective study

Background Methylmalonic acidemia (MMA) is a rare autosomal recessive metabolic disorder caused by defects in the methylmalonyl-CoA mutase or its coenzyme, cobalamin metabolism. The disease presents with nonspecific and diverse clinical manifestations, which complicates early diagnosis. Methods We performed a retrospective analysis of 658 pediatric MMA patients treated at Henan Children’s Hospital between May 2011 and January 2024. The analysis focused on clinical features, genetic mutations, hospitalization trends, and demographic patterns. Results Our study revealed a sex-biased incidence of MMA, with 57.29% male patients. Repeated hospitalizations occurred in 46.96% of cases, and common clinical manifestations included movement disorders, dystonia, vomiting, and respiratory distress. Genetic testing identified MMA caused by MMACHC gene variants and isolated forms caused by MMUT and isolated forms caused by MMUT mutations (MUT gene is synonymous with MMUT). Multisystemic complications were frequent, with notable involvement of the lungs, gastrointestinal system, and kidneys. Geographic clustering was observed, with the majority of patients coming from Henan Province. Conclusions MMA remains a challenging condition to diagnose and treat due to its nonspecific clinical features and the complexity of its genetic mutations. Our findings highlight the importance of early genetic screening and the need for region-specific diagnostic and management strategies. This study provides valuable insights into the epidemiology and clinical management of MMA, supporting the development of improved diagnostic tools and treatment approaches for this rare metabolic disorder.