Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Methylmalonic Acidemia/Aciduria, Vitamin B12 resistant [E71.1]

OMIM numbers:  251000609058 (MUT)

Dipl.-Biol. Birgit Busse

Scientific Background

Vitamin B12 resistant methylmalonic acidemia/aciduria is a rare, autosomal recessive inherited metabolic disorder belonging to the group of organic acidurias, which are characterized by the accumulation of methylmalonic acid and the subsequent increased urinary excretion. It usually appears in the first weeks of life with among other symptoms, recurrent ketoacidotic coma and/or hyperammonemia, episodes of vomiting, dehydration, hypotonia and later developmental disorder.

The vitamin B12-resistant methylmalonic acidemia/aciduria is caused by a deficiency in the mitochondrial vitamin B12 dependent enzyme methylmalonyl-CoA mutase, preventing the degradation of methylmalonyl-CoA to succinyl-CoA. Thus, methylmalonyl-CoA builds up and is converted via an alternative pathway into methylmalonic acid.

Mutations in the methylmalonyl-CoA mutase (MUT) gene lead to a partial (mut-) or complete (mut0) enzyme deficiency. In the later, a substitution with vitamin B12 does not usually alleviate the disease symptoms (vitamin B12-independent form). The symptoms of partial enzyme deficiency (mut-) are usually milder than in complete loss of enzyme activity (mut0).

As well as the vitamin B12-resistant form, various other forms of genetic methylmalonic acidemia/aciduria are known. Furthermore, there is also a form without genetic background caused by a serious alimentary vitamin B12 deficiency.