Methylmalonic acid


Methylmalonic acid is a dicarboxylic acid that is a C-methylated derivative of malonate.
The coenzyme A linked form of methylmalonic acid, methylmalonyl-CoA, is converted into succinyl-CoA by methylmalonyl-CoA mutase, in a reaction that requires vitamin B12 as a cofactor. In this way, it enters the Krebs cycle, and is thus part of one of the anaplerotic reactions.

Pathology

Increased methylmalonic acid levels may indicate a vitamin B12 deficiency. However, it is sensitive but not specific. MMA is elevated in 90–98% of patients with B12 deficiency. It has lower specificity as 20–25% of patients over the age of 70 have elevated levels of MMA, but 25–33% of them do not have B12 deficiency. For this reason, MMA test is not routinely recommended in the elderly.
An excess is associated with methylmalonic acidemia.
MMA concentrations in blood are measured by gas chromatographic mass spectrometry or LC-MS and the expected values of MMA in healthy people are between 73–271 nmol/l.