Phenotypic and genotypic analysis of children with methylmalonic academia: A single-center study in China and a recent literature review

Methylmalonic acidemia (MMA) is a rare inherited metabolic disease caused by methylmalonyl-CoA deficiency or cobalamin metabolism disorder. It is mainly inherited in autosomal recessive mode. According to whether combined with homocysteinemia and the causative genes, it can be divided into many different subtypes. Early diagnosis and early treatment can significantly improve the prognosis. The children with MMA diagnosed in Tianjin Children's Hospital from 2012 to 2020 were collected. All the children underwent comprehensive physical and laboratory examinations. The metabolites in blood and urine were screened by mass spectrometry. Sanger sequencing, Next-generation sequencing and methylation detection were used for gene detection. The detection rate of MMA was 0.20% in children with high-risk of inherited metabolic diseases. The three most common clinical phenotypes of children with MMA were respiratory / metabolic acidosis, global developmental delay and anemia, which were found in 36.00%, 33.33% and 30.67% of children respectively. The most common mutations of MMACHC gene in children with cblC were c.609G > A, c.658_660delAAG and c.80A > G, with frequencies of 34.09%, 13.64% and 13.64%, respectively. This research expands the study of phenotype and genotype of MMA in Chinese population, and can provide reference for clinical diagnosis and treatment of MMA.