{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:37:56Z","timestamp":1791617876903,"version":"4.3.4"},"reference-count":13,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"unspecified","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2021,12,20]]},"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>In clinical practice, the finding of an elevated serum B<jats:sub>12<\/jats:sub> concentration is often the consequence of supplementation with B<jats:sub>12<\/jats:sub> in either oral form or injections. Also, elevated serum B<jats:sub>12<\/jats:sub> may be associated with underlying disorders, like liver diseases or a (haematologic) malignancy. Only a few studies have shown that it may also be the consequence of complex formation of B<jats:sub>12<\/jats:sub>-vitamin binding proteins with immunoglobulins, the so-called macro-B<jats:sub>12<\/jats:sub>. We describe a young woman who previously was diagnosed with B<jats:sub>12<\/jats:sub> deficiency, and in whom, after cessation of B<jats:sub>12<\/jats:sub> injection treatment, neurologic symptoms re-appeared, and despite this, repeatedly elevated serum B<jats:sub>12<\/jats:sub> concentrations above the upper limit of the assay were found. We demonstrated that this was caused by the presence of macro-B<jats:sub>12<\/jats:sub>, which not only resulted in erroneous and longstanding elevated serum B<jats:sub>12<\/jats:sub>, but also masked her underlying B<jats:sub>12<\/jats:sub> deficiency.<\/jats:p>","DOI":"10.1136\/bcr-2021-247660","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T11:20:58Z","timestamp":1642072858000},"page":"e247660","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Macro-B<sub>12<\/sub> masking B<sub>12<\/sub> deficiency"],"prefix":"10.1136","volume":"15","author":[{"given":"Bruce H R","family":"Wolffenbuttel","sequence":"first","affiliation":[{"name":"Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anneke C","family":"Muller Kobold","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Sobczy\u0144ska\u2010Malefora","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences and Medicine, King's College London, London, UK"},{"name":"Nutristasis Unit, Viapath, St Thomas' Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic J","family":"Harrington","sequence":"additional","affiliation":[{"name":"Faculty of Life Sciences and Medicine, King's College London, London, UK"},{"name":"Nutristasis Unit, Viapath, St Thomas' Hospital, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"2025082710440525000_15.1.e247660.1","doi-asserted-by":"crossref","first-page":"17040","DOI":"10.1038\/nrdp.2017.40","article-title":"Vitamin B12 deficiency","volume":"3","author":"Green","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"2025082710440525000_15.1.e247660.2","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1111\/eci.12034","article-title":"Utility and limitations of biochemical markers of vitamin B12 deficiency","volume":"43","author":"Herrmann","year":"2013","journal-title":"Eur J Clin Invest"},{"key":"2025082710440525000_15.1.e247660.3","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.mayocpiqo.2019.03.002","article-title":"The Many Faces of Cobalamin (Vitamin B\n                  12\n               ) Deficiency","volume":"3","author":"Wolffenbuttel","year":"2019","journal-title":"Mayo Clin Proc Innov Qual Outcomes"},{"key":"2025082710440525000_15.1.e247660.4","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/ijlh.12131","article-title":"Immune complexes and persistent high levels of serum vitamin B12","volume":"36","author":"Remacha","year":"2014","journal-title":"Int J Lab Hematol"},{"key":"2025082710440525000_15.1.e247660.5","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2013.204222"},{"key":"2025082710440525000_15.1.e247660.6","doi-asserted-by":"crossref","DOI":"10.3390\/nu10010074","article-title":"Population reference values for serum methylmalonic acid concentrations and its relationship with age, sex, Race-Ethnicity, supplement use, kidney function and serum vitamin B12 in the Post-Folic acid fortification period","volume":"10","author":"Ganji","year":"2018","journal-title":"Nutrients"},{"key":"2025082710440525000_15.1.e247660.7","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.beem.2013.07.002","article-title":"Determination of prolactin: the macroprolactin problem","volume":"27","author":"Fahie-Wilson","year":"2013","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"2025082710440525000_15.1.e247660.8","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.revmed.2009.06.008","article-title":"[Macroenzymes: macro-ASAT and macro-CPK. Two cases and literature review]","volume":"30","author":"Etienne","year":"2009","journal-title":"Rev Med Interne"},{"key":"2025082710440525000_15.1.e247660.9","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2006.073882"},{"key":"2025082710440525000_15.1.e247660.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2009.08.022"},{"key":"2025082710440525000_15.1.e247660.11","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1515\/cclm-2019-0999","article-title":"Macro vitamin B12: an underestimated threat","volume":"58","author":"Soleimani","year":"2020","journal-title":"Clin Chem Lab Med"},{"key":"2025082710440525000_15.1.e247660.12","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/j.1365-2249.1992.tb06880.x","article-title":"Reassessment of the relative prevalences of antibodies to gastric parietal cell and to intrinsic factor in patients with pernicious anaemia: influence of patient age and race","volume":"89","author":"Carmel","year":"1992","journal-title":"Clin Exp Immunol"},{"key":"2025082710440525000_15.1.e247660.13","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.h4416"}],"container-title":["BMJ Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bcr-2021-247660","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T17:44:15Z","timestamp":1756316655000},"score":1,"resource":{"primary":{"URL":"https:\/\/casereports.bmj.com\/lookup\/doi\/10.1136\/bcr-2021-247660"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1]]},"references-count":13,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1,13]]},"published-print":{"date-parts":[[2022,1]]}},"alternative-id":["10.1136\/bcr-2021-247660"],"URL":"https:\/\/doi.org\/10.1136\/bcr-2021-247660","relation":{},"ISSN":["1757-790X"],"issn-type":[{"value":"1757-790X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1]]}}}