gene frequencies of methylmalonic acidemia disease at the global level and compiling the pathogenic mutations in the iranian population

Background: methylmalonic acidemia (mma) is a rare autosomal recessive metabolic disorder resulting from a genetic defect in methylmalonyl-coa mutase (mcm) or a defect in the biosynthesis of its cofactor, adenosyl-cobalamin (adocbl). the disease is caused by a mutation in six main genes (mut, mmaa, mmab, mmadhc, mmachc, and mcee). in this investigation, we estimate mmadisease gene frequencies globally and report mma-causative mutations in the iranian population.methods: human gene mutation database (hgmd) has been utilized to estimate mma-disease gene frequencies. to compile mma mutations in iran, we systematically reviewed pubmed, google scholar, civilica, magiran, and sid databases to explore relevant articles in english and persian.results: the frequencies of causative genes among mma patients at the global level were as follows: mut (64.14%), mmachc (17.74%), mmaa (13.48%), mmab (7.1%), mmadhc (2.9%), and mcee (0.85%). until february 11, 2024, 24 mma mutations had been compiled from the iranian population; of which 11 mutations (45.8%) had been diagnosed only in iran and had not been addressed in other populations yet.conclusion: collection and recognition of mma mutations in the iranian population can be helpful for early diagnosis and treatment before the onset of neurological manifestations in neonates.