{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:01:44Z","timestamp":1792857704176,"version":"4.5.0"},"reference-count":38,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2005,2,16]],"date-time":"2005-02-16T00:00:00Z","timestamp":1108512000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Internal Medicine"],"published-print":{"date-parts":[[2005,3]]},"abstract":"<jats:title>Abstract.<\/jats:title><jats:p><jats:bold>Objectives.\u2002<\/jats:bold> The performance of holotranscobalamin (holoTC) was compared with the other markers of vitamin B<jats:sub>12<\/jats:sub> deficiency, and the influence of age, renal function, and thyroid status was examined.<\/jats:p><jats:p><jats:bold>Design and interventions.\u2002<\/jats:bold> We examined 937 individuals not treated with vitamin B<jats:sub>12<\/jats:sub> but in whom vitamin B<jats:sub>12<\/jats:sub> deficiency was suspected because of a plasma methylmalonic acid (MMA) above 0.28\u2003<jats:italic>\u03bc<\/jats:italic>mol\u2003L<jats:sup>\u22121<\/jats:sup> within the past 4\u2003years. Besides laboratory tests, a structured interview and a neurological examination were performed amongst 534 individuals. Amongst these, 140 individuals qualified for a randomized trial (MMA 0.40\u20132.00\u2003<jats:italic>\u03bc<\/jats:italic>mol\u2003L<jats:sup>\u22121<\/jats:sup>). They were randomized to injections with vitamin B<jats:sub>12<\/jats:sub> or placebo and re\u2010examined after 3\u2003months.<\/jats:p><jats:p><jats:bold>Setting.\u2002<\/jats:bold> One university hospital in Aarhus, Denmark.<\/jats:p><jats:p><jats:bold>Results.\u2002<\/jats:bold> The ROC curves indicate that holoTC (AUC: 0.90) compared favourable with plasma vitamin B<jats:sub>12<\/jats:sub> (AUC: 0.85) for identifying individuals likely to have vitamin B<jats:sub>12<\/jats:sub> deficiency (MMA \u22650.75\u2003<jats:italic>\u03bc<\/jats:italic>mol\u2003L<jats:sup>\u22121<\/jats:sup> and plasma total homocysteine (tHcy) \u226515\u2003<jats:italic>\u03bc<\/jats:italic>mol\u2003L<jats:sup>\u22121<\/jats:sup>), and further that holoTC (AUC: 0.91) might replace combined testing with plasma vitamin B<jats:sub>12<\/jats:sub> and the metabolites. No association was observed between the biochemical markers and symptoms and signs possibly related to vitamin B<jats:sub>12<\/jats:sub> deficiency. HoloTC, TC saturation, plasma vitamin B<jats:sub>12<\/jats:sub>, MMA, and tHcy were significantly associated with plasma creatinine (all with <jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001). Only tHcy was significantly associated with thyroid stimulating hormone (<jats:italic>P<\/jats:italic>\u2003=0.02).<\/jats:p><jats:p><jats:bold>Conclusions.\u2002<\/jats:bold> HoloTC shows promise as first\u2010line tests for diagnosing early vitamin B<jats:sub>12<\/jats:sub> deficiency.<\/jats:p>","DOI":"10.1111\/j.1365-2796.2004.01437.x","type":"journal-article","created":{"date-parts":[[2005,2,16]],"date-time":"2005-02-16T22:40:17Z","timestamp":1108593617000},"page":"289-298","source":"Crossref","is-referenced-by-count":119,"title":["Holotranscobalamin \u2013 a first choice assay for diagnosing early vitamin B<sub>12<\/sub> deficiency?"],"prefix":"10.1111","volume":"257","author":[{"given":"A.\u2010M.","family":"HVAS","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"NEXO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,2,16]]},"reference":[{"key":"e_1_2_19_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830340206"},{"key":"e_1_2_19_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-199107000-00001"},{"key":"e_1_2_19_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1532-5415.1992.tb01939.x"},{"key":"e_1_2_19_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830340205"},{"key":"e_1_2_19_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(80)92287-4"},{"key":"e_1_2_19_7_2","first-page":"829","article-title":"Is there a \u2018\u2018gold standard\u2019\u2019 for human serum vitamin B12 assay","volume":"104","author":"Herbert V","year":"1984","journal-title":"J Lab Clin Med"},{"key":"e_1_2_19_8_2","first-page":"68","article-title":"Who has vitamin B12 deficiency","volume":"108","author":"Schilling RF.","year":"1996","journal-title":"Proceedings of the Association of American Physicians"},{"key":"e_1_2_19_9_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.51.1.357"},{"key":"e_1_2_19_10_2","doi-asserted-by":"crossref","first-page":"1396","DOI":"10.1093\/clinchem\/47.8.1396","article-title":"Vitamin B\u201012 treatment normalizes metabolic markers but has limited clinical effect: a randomized placebo\u2010controlled study","volume":"47","author":"Hvas AM","year":"2001","journal-title":"Clin Chem"},{"key":"e_1_2_19_11_2","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1093\/clinchem\/36.8.1523","article-title":"Methylmalonic acid in renal insufficiency: evidence of accumulation and implications for diagnosis of cobalamin deficiency","volume":"36","author":"Rasmussen K","year":"1990","journal-title":"Clin Chem"},{"key":"e_1_2_19_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2796.2000.00632.x"},{"key":"e_1_2_19_13_2","first-page":"230","article-title":"Plasma homocysteine in renal failure","volume":"40","author":"Hultberg B","year":"1993","journal-title":"Clin Nephrol"},{"key":"e_1_2_19_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/58.4.468"},{"key":"e_1_2_19_15_2","first-page":"332","article-title":"Depletion of serum holotranscobalamin II. 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