Definition: Methylmalonic acidemia is a classical type of organic acidemia.
Methylmalonic acidemia is diagnosed in the early neonatal period, presenting progressive encephalopathy and secondary hyperammonemia. The disorder does not always result in death, if kept under control.
Methylmalonic acid
Methylmalonic acid is involved in the synthesis of adenosylcobalamin (AdoCbl), a coenzyme for methylmalonyl-CoA mutase (MUT) (MIM.609058).
Pathogeny
The inherited form of methylmalonic acidemia causes a defect in the metabolic pathway where methylmalonyl-coenzyme A (CoA) is converted into succinyl-CoA by the enzyme methylmalonyl-CoA mutase.
Vitamin B12
Vitamin B12 is also needed for the conversion of methylmalonyl-CoA to Succinyl-CoA. Mutations leading to defects in vitamin B12 metabolism or in its transport frequently result in the development of methylmalonic acidemia.
A severe nutritional deficiency of vitamin B12 can also result in methylmalonic acidemia. Methylmalonyl CoA requires vitamin B12 to form succinyl-CoA. When the amount of B12 is insufficient for the conversion of cofactor methylmalonyl-CoA into succinyl-CoA, the buildup of unused methylmalonyl-CoA eventually leads to methylmalonic acidemia. This diagnosis is often used as an indicator of vitamin B12 deficiency in serum.
Types
methylmalonic aciduria type cb1A (MIM.251100)
methylmalonic aciduria type cb1B (MIM.251110)
methylmalonic aciduria and homocystinuria type cb1C (MIM.277400)
methylmalonic aciduria and homocystinuria type cb1D (MIM.277410)
methylmalonic aciduria and homocystinuria type cb1F (MIM.277380)
methylmalonic aciduria due to methylmalonyl-CoA mutase deficiency (MIM.251000)
See also
organic acidemias