{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:00:32Z","timestamp":1790593232971,"version":"4.1.0"},"reference-count":87,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1ZIAHG200318"],"award-info":[{"award-number":["1ZIAHG200318"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["BBMRI_CZ LM2023033"],"award-info":[{"award-number":["BBMRI_CZ LM2023033"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NU23\u201007\u201000383"],"award-info":[{"award-number":["NU23\u201007\u201000383"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cobalamin\u2010related remethylation disorders (cbl\u2010RD) are rare, heterogenous conditions with a wide phenotypic spectrum, including prenatal and early infantile manifestations. Data on pregnancy outcomes in affected women and the efficacy and safety of prenatal treatment of affected fetuses remain limited. Here we report (1) five women with cbl\u2010RDs (3 cblC\/epi\u2010cblC, 1 cblD, 1 cblE) who had in total nine pregnancies and (2) eight fetuses with cbl\u2010RD (7 cblC, 1 cblF) diagnosed and treated prenatally. All affected mothers were treated with hydroxocobalamin (OHCbl) during pregnancy and two also received betaine and carnitine. Complications included three preterm deliveries and nephrotic\u2010range proteinuria in one previously undiagnosed mother with cblE. All offspring had favourable outcomes. In pregnancies with affected fetuses, OHCbl was administered to the mother between gestational weeks 5 and 32 at varying doses. Prenatally treated cblC cases exhibited attenuated phenotypes without microcephaly, epilepsy, or severe multisystemic disease. Notably, three of five infants harbouring severe\n                    <jats:italic>MMACHC<\/jats:italic>\n                    variants, who received high\u2010dose pre\u2010 and postnatal OHCbl, exhibited normal neurodevelopment and no maculopathy up to age 2\u20133\u2009years, though variability in genotype, treatment regimens, and duration of follow\u2010up limit generalizability. A literature review identified nine additional pregnancies in women with cbl\u2010RD and seven prenatally treated fetuses, with follow\u2010up available for three. Collectively, our main findings support the safety of maternal and fetal OHCbl treatment during pregnancy. We recommend that when combined with preconception counselling, early standardized diagnosis, optimal monitoring and postnatal care, prenatal OHCbl therapy can improve pregnancy outcomes and mitigate neurodevelopmental and ophthalmic complications in cbl\u2010RD.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70243","type":"journal-article","created":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T14:29:38Z","timestamp":1787754578000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cobalamin\u2010Related Remethylation Disorders: Pregnancy Outcomes and Prenatal Treatment\u2010New Cases and a Literature Study"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0148-6332","authenticated-orcid":false,"given":"Karolina M.","family":"Stepien","sequence":"first","affiliation":[{"name":"Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust  Salford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0762-3721","authenticated-orcid":false,"given":"Jolanta","family":"Sykut\u2010Cegielska","sequence":"additional","affiliation":[{"name":"Department of Inborn Errors of Metabolism and Pediatrics Institute of Mother and Child  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4520-0949","authenticated-orcid":false,"given":"Jennifer","family":"Sloan","sequence":"additional","affiliation":[{"name":"National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1685-2884","authenticated-orcid":false,"given":"Flavia","family":"Piazzon","sequence":"additional","affiliation":[{"name":"Centre de r\u00e9f\u00e9rence maladies h\u00e9r\u00e9ditaires du m\u00e9tabolisme, H\u00f4pital Timone Enfants, APHM  Marseille France"},{"name":"Neurometabolic Unit Children's Institute  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3868-5474","authenticated-orcid":false,"given":"Sarah","family":"Bick","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine, Department of Pediatrics University of Washington and Seattle Children's Hospital  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliette","family":"Bouchereau","sequence":"additional","affiliation":[{"name":"Reference Center for Inborn Error of Metabolism, H\u00f4pital Necker\u2010Enfants Malades, APHP and Universit\u00e9 Paris Cit\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4603-1430","authenticated-orcid":false,"given":"Edwin C.","family":"Ferren","sequence":"additional","affiliation":[{"name":"Wake Forest University School of Medicine, Atrium Health Pediatric Genetics  Charlotte North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0867-722X","authenticated-orcid":false,"given":"Nina","family":"Gold","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics and Metabolism Massachusetts General Hospital for Children  Boston Massachusetts USA"},{"name":"Department of Pediatrics Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-8322","authenticated-orcid":false,"given":"Apolline","family":"Imbard","sequence":"additional","affiliation":[{"name":"Reference Center for Inborn Error of Metabolism, H\u00f4pital Necker\u2010Enfants Malades, APHP and Universit\u00e9 Paris Cit\u00e9  Paris France"},{"name":"Department of Biochemistry H\u00f4pital Necker\u2010Enfants Malades, APHP  Paris France"},{"name":"Paris\u2010Saclay University, CEA, D\u00e9partement M\u00e9dicaments et Technologies pour La Sant\u00e9 (DMTS)  Gif\u2010sur\u2010Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4668-9977","authenticated-orcid":false,"given":"Mirian C. 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