Laboratory assessment of vitamin B12 status

The detection and correction of vitamin B₁₂ (B₁₂) deficiency prevents megaloblastic anaemia and potentially irreversible neuropathy and neuropsychiatric changes. B₁₂ 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 B₁₂ assays measure the sum of haptocorrin-bound and transcobalamin-bound (known as holotranscobalamin) B₁₂ 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 B₁₂ status than serum B₁₂, both assays have an indeterminate range. Biochemical evidence of metabolic abnormalities consistent with B₁₂ insufficiency is frequently detected despite an apparently sufficient abundance of the vitamin. Laboratory B₁₂ status markers that reflect cellular utilisation rather than abundance are available. Two forms of B₁₂ 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 B₁₂ deficiency in folate-replete patients. In the second B₁₂-dependent reaction, methylmalonyl-CoA mutase uses adenosylcobalamin to convert methylmalonyl-CoA to succinyl-CoA. In B₁₂ 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 B₁₂ 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.