Methylmalonic Acid
Overview
Methylmalonic acid (MMA) measures an intermediate metabolite of odd-chain fatty acid, isoleucine, and valine catabolism that accumulates when vitamin B12 is deficient or when methylmalonyl-CoA mutase is defective. Vitamin B12 serves as a cofactor for MMA conversion to succinyl-CoA, a Krebs cycle intermediate; deficiency impairs this step causing MMA accumulation. Elevated MMA specifically indicates functional vitamin B12 deficiency or rare inborn errors of metabolism (methylmalonic acidemia); low levels are not clinically significant. MMA testing provides higher diagnostic specificity than serum B12 for early tissue B12 deficiency detection.Clinical Use Cases
- Confirming tissue-level vitamin B12 deficiency when serum B12 is borderline.
- Diagnosing methylmalonic acidemia and other organic acidemias.
- Differentiating B12 from folate deficiency in megaloblastic anemia.
- Monitoring response to B12 replacement therapy.
Specimen Types
- Serum.
- Plasma.
- Urine.
Measurement Methods
- Gas chromatography-mass spectrometry (GC-MS).
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS).
- Capillary electrophoresis.
Test Preparation and Influencing Factors
- No fasting required; avoid B12 supplements for 1-2 weeks prior.
- Renal impairment elevates serum MMA independent of B12 status.
- Recent vitamin B12 supplementation normalizes MMA rapidly.
- Hemolysis or lipemia interferes with chromatographic methods.
Synonyms
- MMA.
- Methylmalonate.