Late-onset methylmalonic acidemia with a rare MMACHC c.457C>T mutation: a case report and literature review

Background Methylmalonic acidemia (MMA) is a rare autosomal recessive metabolic disorder with heterogeneous clinical phenotypes. The combined form of MMA associated with MMACHC mutations (cblC type) is the most common subtype in China. Late-onset MMA often presents with atypical manifestations, which frequently lead to misdiagnosis and delayed treatment. Case presentation: We report a 13-year-old female patient who presented with progressive cognitive impairment, psychiatric and behavioral abnormalities, and motor dysfunction. Due to atypical clinical features, she was initially misdiagnosed as having autoimmune encephalitis. Laboratory findings revealed markedly elevated plasma homocysteine, decreased methionine, and increased propionylcarnitine with a high propionylcarnitine/acetylcarnitine ratio. Urinary organic acid analysis showed significantly elevated methylmalonic acid and methylcitric acid. Genetic testing identified compound heterozygous mutations in the MMACHC gene: c.482G > A (p.Arg161Gln, maternal) and c.457C > T (p.Arg153Ter), the latter being rarely reported in China. Following treatment with hydroxocobalamin, folate, L-carnitine, and betaine, the patient’s symptoms improved and metabolic abnormalities normalized, although residual cognitive and motor dysfunction persisted. Conclusion This case expands the genotypic spectrum of MMA in China and underscores the importance of metabolic screening and genetic testing in pediatric patients with unexplained neuropsychiatric symptoms. Early recognition and intervention may prevent irreversible neurological sequelae.