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, andMCEE). In this investigation, we estimate MMAdisease gene frequencies globally and report MMA-causative mutations in the Iranian population. Materials and 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.
