Laboratory assessment of vitamin B₁₂ status

The detection and correction of vitamin B 12 (B 12 ) deficiency prevents megaloblastic anaemia and potentially irreversible neuropathy and neuropsychiatric changes. B 12 status is commonly estimated using the abundance of the vitamin in serum, with ∼148 pmol/L (200 ng/L) typically set as the threshold for diagnosing deficiency. Serum B 12 assays measure the sum of haptocorrin-bound and transcobalamin-bound (known as holotranscobalamin) B 12 . It is only holotranscobalamin that is taken up by cells to meet metabolic demand. Although receiver operator characteristic curves show holotranscobalamin measurement to be a moderately more reliable marker of B 12 status than serum B 12 , both assays have an indeterminate range. Biochemical evidence of metabolic abnormalities consistent with B 12 insufficiency is frequently detected despite an apparently sufficient abundance of the vitamin. Laboratory B 12 status markers that reflect cellular utilisation rather than abundance are available. Two forms of B 12 act as coenzymes for two different reactions. Methionine synthase requires methylcobalamin for the remethylation of methionine from homocysteine. A homocysteine concentration >20 µmol/L may suggest B 12 deficiency in folate-replete patients. In the second B 12 -dependent reaction, methylmalonyl-CoA mutase uses adenosylcobalamin to convert methylmalonyl-CoA to succinyl-CoA. In B 12 deficiency excess methylmalonyl-CoA is hydrolysed to methylmalonic acid. A serum concentration >280 nmol/L may suggest suboptimal status in young patients with normal renal function. No single laboratory marker is suitable for the assessment of B 12 status in all patients. Sequential assay selection algorithms or the combination of multiple markers into a single diagnostic indicator are both approaches that can be used to mitigate inherent limitations of each marker when used independently.