{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T23:00:52Z","timestamp":1790550052354,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"S2","license":[{"start":{"date-parts":[[2008,10,29]],"date-time":"2008-10-29T00:00:00Z","timestamp":1225238400000},"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":[[2008,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>It is unusual for inborn errors of metabolism to be considered in the investigative work\u2010up of pancytopenia. We report a family in which the proband presented with failure to thrive at 2 months of age and subsequent bone marrow failure. A previous sibling had died at 7 months of age with suspected leukaemia. Haematological findings in the proband were significant for pancytopenia, and bone marrow aspiration showed dysplastic changes in all cell lineages. Urinary organic acid analysis revealed elevated methylmalonic acid. The synthesis of transcobalamin II (transcobalamin, TC) by cultured fibroblasts was markedly reduced, confirming the diagnosis of TC deficiency. The proband and his younger asymptomatic sister (also found to have TC deficiency) were homozygous for R399X (c.1195C&gt;T), a novel mutation resulting in the loss of the C\u2010 terminal 29 amino acids of TC, a highly conserved region. Response to parenteral vitamin B<jats:sub>12<\/jats:sub> in the proband was dramatic. At 6 years 3 months of age, physical examination is normal and developmental level is age appropriate. His sister is clinically asymptomatic and is also developing normally. Propionylcarnitine concentrations were not elevated in the newborn screening cards from the proband and sister, but that was for specimens retrieved from storage after 7 years and 5 years, respectively. Inherited and acquired cobalamin disorders should both be considered in the differential diagnosis of bone marrow failure syndromes in young children. Early detection of the metabolic causes of bone marrow failure can ensure prompt recovery in some cases involving the vitamin B<jats:sub>12<\/jats:sub> pathway.<\/jats:p>","DOI":"10.1007\/s10545-008-0864-3","type":"journal-article","created":{"date-parts":[[2008,10,27]],"date-time":"2008-10-27T19:44:12Z","timestamp":1225136652000},"page":"287-292","source":"Crossref","is-referenced-by-count":17,"title":["Transcobalamin (TC) deficiency\u2014Potential cause of bone marrow failure in childhood"],"prefix":"10.1002","volume":"31","author":[{"given":"C.","family":"Prasad","sequence":"first","affiliation":[{"name":"Department of Pediatrics Children's Hospital of Western Ontario and the University of Western Ontario London Ontario Canada"},{"name":"Children's Health Research Institute London Ontario Canada"},{"name":"Medical Genetics Program of Southwestern Ontario Children's Hospital, London Health Sciences Centre 800 Commissioners Road East London Ontario N6C 2V5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. S.","family":"Rosenblatt","sequence":"additional","affiliation":[{"name":"Department of Human Genetics McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Corley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Hospital of Western Ontario and the University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. E. L.","family":"Cairney","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Hospital of Western Ontario and the University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. A.","family":"Rupar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Hospital of Western Ontario and the University of Western Ontario London Ontario Canada"},{"name":"Children's Health Research Institute London Ontario Canada"},{"name":"Department of Biochemistry University of Western Ontario London Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,10,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00280489"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320350216"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005507204491"},{"issue":"12","key":"e_1_2_6_5_1","first-page":"ECR45","article-title":"Two newborns with nutritional vitamin B12 deficiency: challenges in newborn screening for vitamin B12 deficiency","volume":"90","author":"Campbell CD","year":"2005","journal-title":"Haematologica"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-199605000-00014"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2007.21"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197111182852103"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1992.tb06410.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01955004"},{"issue":"5","key":"e_1_2_6_11_1","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1542\/peds.65.5.1023","article-title":"The pancytopenia of isovaleric acidemia","volume":"65","author":"Kelleher JF","year":"1980","journal-title":"Pediatrics"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-200205000-00023"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4781(94)90079-5"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2008.01.023"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.63.8.921"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01954389"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0209"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1053\/siny.2001.0087"},{"issue":"1","key":"e_1_2_6_19_1","first-page":"G161","article-title":"Transcobalamin II synthesized in the intestinal villi facilitates transfer of cobalamin to the portal blood","volume":"277","author":"Quadros EV","year":"1999","journal-title":"Am J Physiol"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V85.10.2711.bloodjournal85102711"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0268-960X(87)90033-6"},{"issue":"1","key":"e_1_2_6_22_1","first-page":"19","article-title":"Cobalamin and folate deficiency: acquired and hereditary disorders in children","volume":"36","author":"Rosenblatt DS","year":"1999","journal-title":"Semin Hematol"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/pd.1970070107"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(91)90342-C"},{"issue":"12","key":"e_1_2_6_25_1","first-page":"834","article-title":"A child with vitamin B12 deficiency presenting with pancytopenia and hyperpigmentation","volume":"26","author":"Simsek OP","year":"2004","journal-title":"J Pediatr Hematol Oncol"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198608000-00017"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2006.076679"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509099103"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-008-0864-3","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1007\/s10545-008-0864-3","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-008-0864-3","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T04:22:46Z","timestamp":1694751766000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-008-0864-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,10,29]]},"references-count":27,"journal-issue":{"issue":"S2","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["10.1007\/s10545-008-0864-3"],"URL":"https:\/\/doi.org\/10.1007\/s10545-008-0864-3","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,10,29]]}}}