High Measured Cobalamin (Vitamin B12) Concentration Attributable to an Analytical Problem in Testing Serum from a Patient with Pernicious Anemia

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More than 60 years after the identification of vitamin B12 [cobalamin (Cbl)], both analytical determination and clinical interpretation of its concentration in serum remain troublesome (1)(2)(3). High serum Cbl concentrations frequently occur in myeloproliferative disorders and several hepatic diseases (4). These conditions are seldom associated with signs of Cbl deficiency, but in some cases high serum Cbl concentrations have been associated with clinical evidence of Cbl deficiency related to the presence of antibodies against the Cbl-binding protein transcobalamin (holoTC) or high concentrations of abnormal Cbl-binding proteins (5)(6)(7). We report a case in which an analytical problem within the Immulite 2000 assay [Diagnostic Products Corporation (DPC)] led to a falsely increased Cbl result for a patient presenting with classic hematologic and biochemical features of pernicious anemia. We evaluated a 39-year-old man for macrocytic anemia. Laboratory examination results were as follows: hemoglobin, 6.8 mmol/L (reference interval, 8.4–10.9 mmol/L); mean corpuscular volume, 127 fL (80–100 fL); reticulocytes, 2.7% (0.5%–2.0%); lactate dehydrogenase, 2267 U/L (200–450 U/L); haptoglobin, <58 mg/L (160–2000 mg/L); folic acid, 9.7 nmol/L (6–39 nmol/L); and Cbl, 1199 pmol/L (130–700 pmol/L). Autoantibodies against parietal cells and intrinsic factor (IF) were positive. Because of the likelihood of pernicious anemia, we tested for Cbl deficiency. Increased concentrations of homocysteine [42.7 μmol/L (reference values <15.6 μmol/L)] and methylmalonic acid [2.46 μmol/L (reference values <0.30 μmol/L)] and a decreased concentration of holoTC [<10 pmol/L (reference interval, 55–170 L)] together with concentrations of circulating free holoTC and haptocorrin that were within the reference intervals provided metabolic evidence for Cbl deficiency at the cellular level. After the patient underwent 4 months of treatment with Cbl, the aberrant laboratory findings, including the homocysteine and holoTC concentrations, had returned to reference values.