Methylmalonic Acid, Serum or Plasma

MMA is a four-carbon molecule that is a product of the metabolic break-down of valine, isoleucine, and propionic acid.¹ Vitamin B12 is a critical cofactor for the conversion of MMA to succinate.¹ As a result, vitamin B₁₂ deficiency causes an accumulation of MMA in the serum.¹ MMA concentrations will often become elevated in the early stages of vitamin B₁₂ while serum vitamin B₁₂ levels are in normal range.^1-4 Consequently, MMA measurement is used as a diagnostic test for vitamin B₁₂ deficiency in persons with a low or low normal serum vitamin B₁₂ concentration.^5,6 Follow-up measurement of MMA can also be of value in assessing the effectiveness of vitamin B₁₂ supplementation of deficient patients.⁷

Vitamin B₁₂ deficiency causes macrocytic anemias and decreased erythrocyte survival due to abnormal maturation of erythrocyte precursors in the bone marrow.^10,11 Pernicious anemia is a form of vitamin B₁₂ deficiency that is caused by a lack of intrinsic factor.^10,11 Low vitamin B₁₂ intake, gastrectomy, malabsorption, and transcobalamin deficiency can also cause vitamin B₁₂ deficiency.^10,11 Although severe vitamin B₁₂ deficiency is associated with anemia, hematologic signs are not always observed in patients with biochemically confirmed deficiency.¹² Elderly patients with cobalamin deficiency may present with peripheral neuropathy, ataxia, memory impairment, depression, and dementia in the absence of anemia.^13,14

A generally agreed on cutoff for elevated plasma MMA is 370 nmol/L.^6,12 Approximately 2% of the US population and 7% of elderly persons have MMA concentrations above this threshold.¹²