{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:21:05Z","timestamp":1775841665786,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2010,3,30]],"date-time":"2010-03-30T00:00:00Z","timestamp":1269907200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2010,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Transcobalamin (transcobalamin II, TC) transports plasma vitamin B<jats:sub>12<\/jats:sub> (cobalamin, Cbl) into cells. TC deficiency is a rare autosomal recessive disorder causing intracellular Cbl depletion, which in turn causes megaloblastic bone marrow failure, accumulation of homocysteine and methylmalonic acid, and methionine depletion. The clinical presentation reflects intracellular Cbl defects, with early\u2010onset failure to thrive with gastrointestinal symptoms, pancytopenia, and megaloblastic anemia, sometimes followed by neurological complications. We report the clinical, biological, and molecular findings and the outcome in five TC\u2010deficient patients. The three treated early had an initial favorable outcome, whereas the two treated inadequately had late\u2010onset severe neuro\u2010ophthalmological impairment. Even if the natural course of the disease over time might also result in late\u2010onset symptoms in the aggressively treated patients, these data emphasize that TC deficiency is a severe disorder requiring early detection and probably long\u2010term aggressive therapy. Mutation analysis revealed six unreported mutations in the<jats:italic> TCN2<\/jats:italic> gene. <jats:italic>In silico<\/jats:italic> structural analysis showed that these mutations disrupt the Cbl\u2010TC interaction domain and\/or the putative transcobalamin\u2013transcobalamin receptor interaction domain.<\/jats:p>","DOI":"10.1007\/s10545-010-9074-x","type":"journal-article","created":{"date-parts":[[2010,3,29]],"date-time":"2010-03-29T14:20:00Z","timestamp":1269872400000},"page":"223-229","source":"Crossref","is-referenced-by-count":29,"title":["Should transcobalamin deficiency be treated aggressively?"],"prefix":"10.1002","volume":"33","author":[{"given":"Manuel","family":"Schiff","sequence":"first","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence Maladies M\u00e9taboliques CHU Robert Debr\u00e9 APHP Paris France"},{"name":"Manuel Schiff, Service de Neurop\u00e9diatrie &amp; Maladies M\u00e9taboliques, Centre de r\u00e9f\u00e9rence Maladies M\u00e9taboliques H\u00f4pital Robert Debr\u00e9 48, boulevard S\u00e9rurier Paris 75019 France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H\u00e9l\u00e8ne","family":"Ogier de Baulny","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence Maladies M\u00e9taboliques CHU Robert Debr\u00e9 APHP Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghislaine","family":"Bard","sequence":"additional","affiliation":[{"name":"AP\u2010HP, Laboratoire d'H\u00e9matologie H\u00f4pital Henri Mondor Cr\u00e9teil France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Barlogis","sequence":"additional","affiliation":[{"name":"H\u00e9matologie P\u00e9diatrique, CHU Timone Enfants Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Hamel","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence affections sensorielles g\u00e9n\u00e9tiques CHU Montpellier 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