Methylmalonic Acid (MMA)

Reference Intervals

• Canine: 415−1,193 nmol/L
• Feline: 139−898 nmol/L

Sample Requirements & Shipping Information

• 0.5 mL of serum (non-hemolyzed); fasting (8 to 12 hours) is recommended.
• Samples should be frozen prior to and during shipment to lab.

Turnaround

• 1-6 business days after receipt of samples.
• Samples typically run on Thursdays only.

General Information

Methylmalonic acid (MMA) is a marker for cobalamin deficiency on a cellular level and when quantified, should be measured in conjunction with cobalamin (vitamin B₁₂). Cobalamin is an essential cofactor for the enzyme L-methylmalonyl CoA mutase, which converts L-methylmalonyl CoA to succinyl CoA. When dogs or cats are cobalamin deficient, the physiologic metabolic pathway is reversed, and the production of MMA is favored. Measurement of serum MMA (sMMA) concentration can be used to diagnose cobalamin deficiency in patients that have a low normal serum cobalamin concentration. Cellular cobalamin concentrations are more representative of the true cellular cobalamin status than serum cobalamin concentrations because the cobalamin-dependent biochemical reactions occur intracellularly. In a recent study evaluating cobalamin and sMMA in puppies with parvovirus and other nonviral acute enteropathies, sMMA remained normal despite these puppies showing significantly lower serum cobalamin concentrations compared to age matched healthy controls. This lends credence to the specificity of sMMA for true cellular cobalamin deficiency. Since MMA is renally excreted, increased concentrations should be interpreted cautiously in patients with renal failure.

Further Reading

1. Ruaux CG, Steiner JM, Williams DA. Metabolism of amino acids in cats with severe cobalamin deficiency. American Journal of Veterinary Research 2001;62:1852-1858.
2. Stabler SP, Marcell PD, Podell ER, Allen RH, Lindenbaum J. Assay of methylmalonic acid in the serum of patients with cobalamin deficiency using capillary gas chromatography-mass spectrometry. Journal of Clinical Investigation1986;77:1606-1612.
3. Ruaux CG, Steiner JM, Williams DA. Relationships between low serum cobalamin concentrations and methylmalonic acidemia in cats. Journal of Veterinary Internal Medicine 2009;23:472-475.
4. Berghoff N, Suchodolski JS, Steiner JM. Association between serum cobalamin and methylmalonic acid concentrations in dogs. Veterinary Journal2012;191:306–311.
5. Berghoff N, Parnell NK, Hill S, Suchodolski JS, Steiner JM. Serum cobalamin and methylmalonic acid concentrations in dogs with chronic gastrointestinal disease. American Journal of Veterinary Research 2013;74:84-89.
6. Hung M, Heinz J, Steiner JM, Suchodolski JS, Lidbury JA. Serum cobalamin and methylmalonic acid concentrations in juvenile dogs with parvoviral enteritis or other acute enteropathies. Journal of Veterinary Internal Medicine 2023;37:1368-1375.