Methylmalonic aciduria and Vitamin B12

Methylmalonic aciduria encompasses a diverse spectrum of congenital metabolic disorders characterized by the accumulation of methylmalonic acid in bodily fluids and tissues. This condition, demonstrating clinical similarities to propionic acidaemia, arises from a deficiency in either methylmalonyl-CoA mutase or its coenzyme, adenosylcobalamin, also referred to as coenzyme B12.

Adenosylcobalamin, a biologically active variant of vitamin B12, alongside methylcobalamin, assumes a crucial role in the functioning of methylmalonyl-CoA mutase. Encoded by the MUT gene, this enzyme facilitates the conversion of methylmalonyl-CoA into succinyl-CoA in humans. Mutations in the MUT gene can give rise to various manifestations of methylmalonic aciduria.

The proper operation of the mutase enzyme relies on adenosylcobalamin as a coenzyme, establishing a close link between the integrity of methylmalonic acid metabolism and the sufficient intake, precise absorption, transportation, and intracellular processing of vitamin B12 (cobalamin). Deficiencies in methylmalonyl-CoA mutase result in heightened levels of methylmalonic acid in bodily fluids.
Methylmalonic aciduria and Vitamin B12