Isotope-Dilution Assay for Urinary Methylmalonic Acid in the Diagnosis of Vitamin B₁₂ Deficiency

Abstract

Vitamin B₁₂ deficiency is a frequently considered diagnosis for which there is no single, commonly available and accurate test. A urinary methylmalonic acid assay using gas chromatography-mass spectrometry has been proposed as the preferred test. We reviewed vitamin B₁₂ assays on 1599 consecutive patients and prospectively studied all patients with low serum B₁₂ levels (n = 75) and a random sample of patients with normal levels (n = 68). Of 96 evaluable patients, 7 had clinical deficiency. All 7 deficient patients had urinary methylmalonic acid levels greater than 5 µ/mg creatinine (sensitivity, 100%; confidence interval, 65% to 100%). Of the 89 patients who were not clinically deficient, 88 had urinary methylmalonic acid levels less than or equal to 5 µ/mg creatinine (specificity, 99%). The overall test accuracy in this population was 99%. If the high sensitivity and specificity of the gas chromatography-mass spectrometry assay for urinary methylmalonic acid is supported by other clinical studies, the methylmalonic acid assay may become the reference standard for the diagnosis of vitamin B₁₂ deficiency.