Methylmalonic Acidemia (MMA) is a rare autosomal recessive metabolic disorder, result from genetic defect in methylmalonyl-CoA mutase (MCM) enzyme. This enzyme is necessary in the catabolism of branched chain amino acids (BCAA) for the degradation of oddchain fatty acids, the amino acid valine, isoleucine, methionine, and threonine, and cholesterol. MMA has wide range of clinical manifestations varying from no signs or symptoms to severe lethargy and metabolic crisis in newborn infants. This disease is caused by mutation in five mainly genes (MUT, MMAA, MMAB, MMADHC, MCEE). In this study we reported a recurrent MMA causative mutation in 2 years old boy. Materials and Methods: We performed whole exome sequencing method (WES), followed by Sanger sequence in our patient. In silico analyses of the identified variant was performed using web-based bioinformatics programs. Results: WES identified the missense mutation c.A976G (p.R326G) in the MUT gene which affects the stability and enzymatic activity of MCM. The results of the Sanger sequence showed that our patient is homozygous and his parents are carriers. Bioinformatics software programs such as Polyphen, SIFT have predicted that this variant will be damaging. Conclusion: This pathogenic mutation has previously been reported in Iran and Ukraine. Considering that our patient is from the northern Iran and this mutation has been already reported the same region; Therefore we can conclude that this mutation is recurrent and prevalent in north of Iran. Additionally, our finding would be beneficial for prenatal diagnosis of MMA as well as establishing a local variant database.
