{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:58:06Z","timestamp":1789696686420,"version":"4.0.1"},"reference-count":52,"publisher":"BMJ","issue":"2","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2016,4,20]]},"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:p>The detection and correction of vitamin B<jats:sub>12<\/jats:sub> (B<jats:sub>12<\/jats:sub>) deficiency prevents megaloblastic anaemia and potentially irreversible neuropathy and neuropsychiatric changes. B<jats:sub>12<\/jats:sub> status is commonly estimated using the abundance of the vitamin in serum, with \u223c148\u2005pmol\/L (200\u2005ng\/L) typically set as the threshold for diagnosing deficiency. Serum B<jats:sub>12<\/jats:sub> assays measure the sum of haptocorrin-bound and transcobalamin-bound (known as holotranscobalamin) B<jats:sub>12<\/jats:sub>. 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<jats:sub>12<\/jats:sub> status than serum B<jats:sub>12<\/jats:sub>, both assays have an indeterminate range. Biochemical evidence of metabolic abnormalities consistent with B<jats:sub>12<\/jats:sub> insufficiency is frequently detected despite an apparently sufficient abundance of the vitamin. Laboratory B<jats:sub>12<\/jats:sub> status markers that reflect cellular utilisation rather than abundance are available. Two forms of B<jats:sub>12<\/jats:sub> act as coenzymes for two different reactions. Methionine synthase requires methylcobalamin for the remethylation of methionine from homocysteine. A homocysteine concentration &gt;20\u2005\u00b5mol\/L may suggest B<jats:sub>12<\/jats:sub> deficiency in folate-replete patients. In the second B<jats:sub>12<\/jats:sub>-dependent reaction, methylmalonyl-CoA mutase uses adenosylcobalamin to convert methylmalonyl-CoA to succinyl-CoA. In B<jats:sub>12<\/jats:sub> deficiency excess methylmalonyl-CoA is hydrolysed to methylmalonic acid. A serum concentration &gt;280\u2005nmol\/L may suggest suboptimal status in young patients with normal renal function. No single laboratory marker is suitable for the assessment of B<jats:sub>12<\/jats:sub> 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.<\/jats:p>","DOI":"10.1136\/jclinpath-2015-203502","type":"journal-article","created":{"date-parts":[[2016,5,12]],"date-time":"2016-05-12T00:09:05Z","timestamp":1463011745000},"page":"168-173","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":98,"title":["Laboratory assessment of vitamin B<sub>12<\/sub> status"],"prefix":"10.1136","volume":"70","author":[{"given":"Dominic J","family":"Harrington","sequence":"first","affiliation":[{"name":"The Nutristasis Unit, St Thomas\u2019 Hospital NHS Foundation Trust, London, UK"},{"name":"Division of Women's Health, School of Medicine, King's College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2016,5,11]]},"reference":[{"key":"2025092510175047000_70.2.168.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1113996"},{"key":"2025092510175047000_70.2.168.2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g5226"},{"key":"2025092510175047000_70.2.168.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198806303182604"},{"key":"2025092510175047000_70.2.168.4","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.161.12.1534"},{"key":"2025092510175047000_70.2.168.5","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12959"},{"key":"2025092510175047000_70.2.168.6","doi-asserted-by":"crossref","unstructured":"Vakur Bor M , Nexo E . 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