Objectives: To develop a precise and sensitive assay for methylmalonic acid (MMA) using positive chemical ionization gas chromatography mass spectrometry (CI GC-MS), and to illustrate its clinical utility.
Methods: Using the developed assay, reference intervals were determined with 108 ambulatory individuals, and potential clinical utility examined in 178 consecutive patients with possible cobalamin deficiency (serum B12<200 nmol/L).
Results and conclusions: Methylmalonic acid measured by CI GC-MS was precise (CV: 4-5%), and sensitive (limit of quantitation: 37 nmol/L). In a clinical reference set, 37% of individuals with serum B12 less than 200 pmol/L had plasma MMA concentrations within the reference interval (75-378 nmol/L), rendering cobalamin deficiency unlikely. The observation illustrates that MMA assay may be a useful adjunct test in assessing patients with low serum B12.