Methylmalonic acidemia, vitamin B12 resistant, type mutant

Vitamin B12-responive methylmalonic acidemia describes an autosomal recessive metabolic disorder that belongs to the group of organoacidopathies.

It is characterized by an accumulation and increased renal excretion of methylmalonic acid and does not respond to treatment with vitamin B12. The disease manifests already in the newborn or infancy and is characterized by recurrent coma, dehydration, mental retardation, hypotonia and episodic vomiting.

The cause is a mutation in the MUT gene at the locus 6p21, which codes for the enzyme methylmalonyl-CoA mutase. There is a lack of activity of the B12-dependent enzyme, which does not degrade methylmalonyl-CoA to succinyl-CoA properly. The accumulation of methylmalonyl-CoA is converted to methylmalonic acid.

The more extreme form is the clinical picture of complete loss of enzyme activity (mut0).