Impaired Function of a Rare Mutation in the Gene Causes Methylmalonic Acidemia in a Chinese Patient.

Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disorder mainly caused by mutations in the methylmalonyl coenzyme A mutase (MCM) gene () and leads to the reduced activity of MCM. In this study, a 3-year-old girl was diagnosed with carnitine deficiency secondary to methylmalonic acidemia by tandem mass spectrometry (MS/MS) and gas chromatography/mass spectrometry (GS/MS). Whole-exome sequencing (WES) was performed on the patient and identified two compound heterozygous mutations in : c.554C>T (p. S185F) and c.729-730insTT (p. D244Lfs 39). Bioinformatics analysis predicted that the rare missense mutation of c.554C>T would be damaging. Moreover, this rare mutation resulted in the reduced levels of mRNA and MMUT protein. Collectively, our findings provide a greater understanding of the effects of variants and will facilitate the diagnosis and treatment of patients with MMA.