{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:26:19Z","timestamp":1791325579996,"version":"4.3.1"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2011,6,1]],"date-time":"2011-06-01T00:00:00Z","timestamp":1306886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Fisheries and Food and the Health Research Board"},{"name":"Food for Health Research Initiative"},{"name":"Axis-Shield Diagnostics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,6,1]]},"abstract":"<jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Vitamin B12 deficiency is common among the elderly, and early detection is clinically important. However, clinical signs and symptoms have limited diagnostic accuracy and there is no accepted reference test method.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>In elderly subjects (n = 700; age range 63\u201397 years), we investigated the ability of serum cobalamin, holotranscobalamin (holoTC), total homocysteine (tHcy), methylmalonic acid (MMA), serum and erythrocyte folate, and other hematologic variables to discriminate cobalamin deficiency, defined as red blood cell cobalamin &amp;lt;33 pmol\/L.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Serum holoTC was the best predictor, with area under the ROC curve (95% CI) 0.90 (0.86\u20130.93), and this was significantly better (P \u2264 0.0002) than the next best predictors; serum cobalamin, 0.80 (0.75\u20130.85), and MMA, 0.78 (0.72\u20130.83). For these 3 analytes, we constructed a 3-zone partition of positive and negative zones and a deliberate indeterminate zone between. The boundaries were values of each test that resulted in a posttest probability of deficiency of 60% and a posttest probability of no deficiency of 98%. The proportion of indeterminate observations for holoTC, cobalamin, and MMA was 14%, 45%, and 50%, respectively. Within the holoTC indeterminate zone (defined as 20\u201330 pmol\/L), discriminant analysis selected only erythrocyte folate, which correctly allocated 65% (58\/89) of the observations. Renal dysfunction compromised the diagnostic accuracy of MMA but not holoTC or serum cobalamin.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>This study supports the use of holoTC as the first-line diagnostic procedure for vitamin B12 status.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1373\/clinchem.2010.158154","type":"journal-article","created":{"date-parts":[[2011,4,12]],"date-time":"2011-04-12T01:54:04Z","timestamp":1302573244000},"page":"856-863","source":"Crossref","is-referenced-by-count":108,"title":["Diagnostic Accuracy of Holotranscobalamin, Methylmalonic Acid, Serum Cobalamin, and Other Indicators of Tissue Vitamin B12 Status in the Elderly"],"prefix":"10.1093","volume":"57","author":[{"given":"Edward","family":"Valente","sequence":"first","affiliation":[{"name":"Axis-Shield Diagnostics, Dundee, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M","family":"Scott","sequence":"first","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Republic of Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per-Magne","family":"Ueland","sequence":"first","affiliation":[{"name":"Section for Pharmacology, Institute of Medicine, University of Bergen, and Laboratory of Clinical Biochemistry, Haukeland University Hospital, Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conal","family":"Cunningham","sequence":"first","affiliation":[{"name":"Mercers Institute for Research on Aging, St James Hospital, Dublin, Republic of Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Casey","sequence":"first","affiliation":[{"name":"Mercers Institute for Research on Aging, St James Hospital, Dublin, Republic of Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne M","family":"Molloy","sequence":"first","affiliation":[{"name":"School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Republic of Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,6,1]]},"reference":[{"key":"2020022705121357800_B1","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1001\/archinte.1988.00380080016007","article-title":"Pernicious anemia: the expected findings of very low serum cobalamin levels, anemia and macrocytosis are often lacking","volume":"148","author":"Carmel","year":"1988","journal-title":"Arch Intern Med"},{"key":"2020022705121357800_B2","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1056\/NEJM198806303182604","article-title":"Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or 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