{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:25:21Z","timestamp":1780507521615,"version":"3.54.1"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T00:00:00Z","timestamp":1713139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Methionine synthase reductase deficiency (cblE) is a rare autosomal recessive inborn error of cobalamin metabolism caused by pathogenic variants in the methionine synthase reductase gene (<jats:italic>MTRR<\/jats:italic>). Patients usually exhibit early\u2010onset bone marrow failure with pancytopenia including megaloblastic anemia. The latter can remain isolated or patients may present developmental delay and rarely macular dysfunction. Treatment mostly includes parenteral hydroxocobalamin to maximize the residual enzyme function and betaine to increase methionine concentrations and decrease homocysteine accumulation. We report herein 2 cblE siblings diagnosed in the neonatal period with isolated pancytopenia who, despite treatment, exhibited in adulthood hemolytic anemia (LDH &gt;11\u2009000\u2009U\/L, undetectable haptoglobin, elevated unconjugated bilirubin) which could finally be successfully treated by hydroxocobalamin dose escalation. There was no obvious trigger apart from a parvovirus B19 infection in one of the patients. This is the first report of such complications in adulthood. The use of LDH for disease monitoring could possibly be an additional useful biomarker to adjust hydroxocobalamin dosage. Bone marrow infection with parvovirus B19 can complicate this genetic disease with erythroblastopenia even in the absence of an immunocompromised status, as in other congenital hemolytic anemias. The observation of novel hemolytic features in this rare disease should raise awareness about specific complications in remethylation disorders and plea for hydroxocobalamin dose escalation.<\/jats:p>","DOI":"10.1002\/jmd2.12422","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T07:46:00Z","timestamp":1713167160000},"page":"163-170","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Late\u2010onset refractory hemolytic anemia in siblings treated for methionine synthase reductase deficiency: A rare complication possibly prevented by hydroxocobalamin dose escalation?"],"prefix":"10.1002","volume":"65","author":[{"given":"Alexandre","family":"Nguyen","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology Normandie Univ, UNICAEN, CHU Caen Normandie  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Deshayes","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Clinical Immunology Normandie Univ, UNICAEN, CHU Caen Normandie  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Nowoczyn","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory CHU Caen Normandie  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apolline","family":"Imbard","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory Necker University Hospital, APHP  Paris France"},{"name":"D\u00e9partement M\u00e9dicaments et Technologies Pour la Sant\u00e9 (DMTS) Universit\u00e9 Paris\u2010Saclay, CEA, INRAE, MetaboHUB  Gif\u2010sur\u2010Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lamisse","family":"Mansour\u2010Hendili","sequence":"additional","affiliation":[{"name":"LBM SeqOIA  Paris France"},{"name":"Department of Genetics Henri Mondor Hospital, APHP  Cr\u00e9teil France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Cesbron","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory CHU Caen Normandie  Caen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Fran\u00e7ois","family":"Benoist","sequence":"additional","affiliation":[{"name":"Biochemistry Laboratory Necker University Hospital, APHP  Paris France"},{"name":"D\u00e9partement M\u00e9dicaments et Technologies Pour la Sant\u00e9 (DMTS) Universit\u00e9 Paris\u2010Saclay, CEA, INRAE, MetaboHUB  Gif\u2010sur\u2010Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8272-232X","authenticated-orcid":false,"given":"Manuel","family":"Schiff","sequence":"additional","affiliation":[{"name":"Reference Center for Inherited Metabolic Diseases Necker University Hospital, APHP and University of Paris Cit\u00e9  Paris France"},{"name":"INSERM UMRS_1163, Institut Imagine  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,4,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12012"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-016-9991-4"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20104658.2009.06919.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/ic010802a"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2013.12.030"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1021299117308"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545\u2010014\u20109803\u20107"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-010-9120-8"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005\u20102744(71)90247\u20106"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(81)90650-4"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102362.1996.122254.x"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356\u2010021\u201013014\u20105"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20104658.2006.05583.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009\u20102797(94)03339\u2010a"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1254\/jjp.27.596"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3233\/CH\u20102010\u20101284"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2004.08.005"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.2001.280.4.C867"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0891\u20105849(03)00435\u20100"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.11.022"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.3121\/cmr.4.3.236"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.19.1.51"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.21307\/immunohematology-2020-046"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.revmed.2006.10.319"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9571072"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.15.3.485\u2010505.2002"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2019.05.009"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1177\/00236772211062861"},{"key":"e_1_2_7_30_1","first-page":"307","article-title":"Diagnosing human parvovirus B19 infection: guidelines for test selection","volume":"6","author":"Jordan JA","year":"2001","journal-title":"Mol Diagn J Devoted Underst Hum Dis Clin Appl Mol Biol"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V49.6.987.987"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0248\u20108663(01)00481\u20107"}],"container-title":["JIMD Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12422","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,9]],"date-time":"2024-05-09T02:34:11Z","timestamp":1715222051000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.12422"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,15]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1002\/jmd2.12422"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.12422","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,15]]},"assertion":[{"value":"2024-02-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}