title: Laboratory assessment of vitamin B12 status.
abstract: The detection and correction of vitamin B12(B12) deficiency prevents megaloblastic anaemia and potentially irreversible neuropathy and neuropsychiatric changes. B12status 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 B12assays measure the sum of haptocorrin-bound and transcobalamin-bound (known as holotranscobalamin) B12It 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 B12status than serum B12, both assays have an indeterminate range. Biochemical evidence of metabolic abnormalities consistent with B12insufficiency is frequently detected despite an apparently sufficient abundance of the vitamin. Laboratory B12status markers that reflect cellular utilisation rather than abundance are available. Two forms of B12act 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 B12deficiency in folate-replete patients. In the second B12-dependent reaction, methylmalonyl-CoA mutase uses adenosylcobalamin to convert methylmalonyl-CoA to succinyl-CoA. In B12deficiency 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 B12status 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.
authors.affiliation: The Nutristasis Unit, St Thomas' Hospital NHS Foundation Trust, London, UK.|Division of Women's Health, School of Medicine, King's College London, London, UK.
authors.forename: Dominic J
authors.initials: DJ
authors.lastname: Harrington
mesh_terms: D015415:Biomarkers / Q000097:blood; D006801:Humans; D014805:Vitamin B 12 / Q000097:blood*; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D014805:Vitamin B 12
keywords: B12; COBALAMIN; DIAGNOSIS; LABORATORY TESTS