Methylmalonic aciduria type A protein, mitochondrial (MMAA)

Methylmalonic aciduria type A protein, mitochondrial (MMAA) is a mitochondrial GTPase essential for the intracellular metabolism of cobalamin (vitamin B12). It facilitates translocation and final processing of cobalamin to adenosylcobalamin (AdoCbl), the cofactor required by methylmalonyl-CoA mutase, a key enzyme in the breakdown of certain amino acids and fatty acids. MMAA functions as a chaperone, stabilizing methylmalonyl-CoA mutase and protecting it from inactivation, in addition to promoting active cofactor insertion. Mutations in the MMAA gene lead to the metabolic disorder methylmalonic acidemia (cblA type), characterized primarily by accumulation of methylmalonic acid and multiple systemic symptoms. There are no known drugs that directly target MMAA. Management of MMAA deficiency is typically through dietary management, vitamin B12 derivatives for responsive cases, and supportive metabolic therapies[1][2][3][6][8][9].

Other names

MMAAcblAMethylmalonic aciduria (cobalamin deficiency) cblA typeLINC02491 (note: rarely used, usually refers to a long non-coding RNA at the same locus)Methylmalonic aciduria type A proteinMutant adenosylcobalamin protein

Supplementation (hydroxocobalamin, a vitamin B12 analog, is given to bypass metabolic blocks downstream of MMAA deficiency; improves AdoCbl supply and methylmalonyl-CoA mutase function). No small-molecule effectors, inhibitors, or direct-acting drugs targeting MMAA[3][6]