{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:25:23Z","timestamp":1780507523586,"version":"3.54.1"},"reference-count":13,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:00:00Z","timestamp":1686873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012505","name":"Royal Perth Hospital Medical Research Foundation","doi-asserted-by":"publisher","award":["MR\/T008024\/1"],"award-info":[{"award-number":["MR\/T008024\/1"]}],"id":[{"id":"10.13039\/100012505","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019256","name":"NIHR Great Ormond Street Hospital Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019256","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Isolated remethylation defects are rare inherited diseases caused by a defective remethylation of homocysteine to methionine, preventing various essential methylation reactions to occur. Patients present with a systemic phenotype, which can especially affect the central and peripheral nervous systems leading to epileptic encephalopathy, developmental delay and peripheral neuropathy. Respiratory failure has been described in some cases, caused by both central and peripheral neurological involvement. In published cases, the genetic diagnosis and initiation of appropriate therapy were rapidly performed following respiratory failure and led to a rapid recovery of respiratory insufficiency within days. Here, we present two infantile\u2010onset cases of isolated remethylation defects, cobalamine (Cbl)G and methylenetetrahydrofolate reductase (MTHFR) deficiencies, which were diagnosed after several months of respiratory failure. Disease modifying therapy based on hydroxocobalamin and betaine was initiated and shows a progressive improvement and enabled weaning off respiratory support after 21 and 17\u2009months in CblG and MTHFR patients respectively. We show that prolonged respiratory failure responds to conventional therapy in isolated remethylation defects, but can require a sustained period of time before observing a full response to therapy.<\/jats:p>","DOI":"10.1002\/jmd2.12375","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T09:33:38Z","timestamp":1686908018000},"page":"274-281","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Prolonged respiratory failure responds to conventional therapy in isolated homocysteine remethylation defects"],"prefix":"10.1002","volume":"64","author":[{"given":"Abigail","family":"Whitehouse","sequence":"first","affiliation":[{"name":"Department of Paediatric Respiratory Medicine, Barts Health NHS Trust Royal London Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Preeya","family":"Rehsi","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Hartley","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology Barts Health NHS Trust, Royal London Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Grunewald","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berna Seker","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Great Ormond Street Institute of Child Health University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Pegoretti Baruteau","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology University College London Hospitals NHS Foundation Trust  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayhan","family":"Yaman","sequence":"additional","affiliation":[{"name":"Department of Paediatric Intensive Care Unit \u0130stinye \u00dcniversite Hastanesi Liv Hospital  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suren","family":"Thavagnanam","sequence":"additional","affiliation":[{"name":"Department of Paediatric Respiratory Medicine, Barts Health NHS Trust Royal London Hospital  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0582-540X","authenticated-orcid":false,"given":"Julien","family":"Baruteau","sequence":"additional","affiliation":[{"name":"Department of Metabolic Medicine Great Ormond Street Hospital for Children NHS Foundation Trust  London UK"},{"name":"Great Ormond Street Institute of Child Health University College London  London 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Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmd2.12375","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T22:14:13Z","timestamp":1692483253000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmd2.12375"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,16]]},"references-count":13,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/jmd2.12375"],"URL":"https:\/\/doi.org\/10.1002\/jmd2.12375","archive":["Portico"],"relation":{},"ISSN":["2192-8312","2192-8312"],"issn-type":[{"value":"2192-8312","type":"print"},{"value":"2192-8312","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,16]]},"assertion":[{"value":"2023-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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