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The relationship between clinically confirmed cobalamin deficiency and serum methylmalonic acid

Abstract. Over a 1‐year period, we examined 42 consecutive patients with low serum cobalamin levels detected by primary screening test (S‐protein binder, RIA). In 31 patients (74%) clinical cobalamin deficiency was confirmed, whereas the remaining 11 patients (26%) were characterized clinically as non‐cobalamin deficient. The serum methylmalonic acid level was higher than 0.34 μmol l−1 (3 SD above the mean in normal controls) in 30 of the 31 clinically characterized cobalamin‐deficient subjects, and below this level in 10 of the 11 non‐deficient patients. We conclude that the serum methylmalonic acid assay provides an appropriate means of discrimination between cobalamin deficiency and non‐cobalamin deficiency (efficiency=0.95), and we recommend that the assay be adopted as the standard test for diagnosis of tissue cobalamin deficiency.