{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T20:30:23Z","timestamp":1788899423281,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T00:00:00Z","timestamp":1723852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cobalamin C (Cbl\u2010C) defect causes methylmalonic acidemia, homocystinuria, intellectual disability and visual impairment, despite treatment adherence. While international guidelines recommend parenteral hydroxocobalamin (OH\u2010Cbl) as effective treatment, dose adjustments remain unclear. We assessed OH\u2010Cbl therapy impact on biochemical, neurocognitive and visual outcomes in early\u2010onset Cbl\u2010C patients treated with different OH\u2010Cbl doses over 3\u2009years. Group A (<jats:italic>n<\/jats:italic>\u2009=\u20095), diagnosed via newborn screening (NBS), received high\u2010dose OH\u2010Cbl (median 0.55\u2009mg\/kg\/day); Group B1 (<jats:italic>n<\/jats:italic>\u2009=\u20093), NBS\u2010diagnosed, received low\u2010dose OH\u2010Cbl (median 0.09\u2009mg\/kg\/day); Group B2 (<jats:italic>n<\/jats:italic>\u2009=\u200912), diagnosed on clinical bases, received low\u2010dose OH\u2010Cbl (median 0.06\u2009mg\/kg\/day). Biochemical analyses revealed better values of homocysteine, methionine and methylmalonic acid in Group A compared to Group B1 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05 and <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01, respectively) and B2 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01 and <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, respectively). Neurodevelopmental assessment showed better outcome in Group A compared to low\u2010dose treated Groups B1 and B2, especially in Developmental Quotient, Hearing and Speech and Performance subscales without significant differences between Group B2 and Group B1. Maculopathy was detected in 100%, 66% and 83% of patients in the three groups, respectively. This study showed that \u201chigh\u2010dose\u201d OH\u2010Cbl treatment in NBS\u2010diagnosed children with severe early\u2010onset Cbl\u2010C defect led to a significant improvement in the metabolic profile and in neurocognitive outcome, compared to age\u2010matched patients treated with a \u201clow\u2010dose\u201d regimen. Effects on maculopathy seem unaffected by OH\u2010Cbl dosage. Our findings, although observed in a limited number of patients, may contribute to improve the long\u2010term outcome of Cbl\u2010C patients.<\/jats:p>","DOI":"10.1002\/jimd.12787","type":"journal-article","created":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T05:30:47Z","timestamp":1723872647000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Improved biochemical and neurodevelopmental profiles with high\u2010dose hydroxocobalamin therapy in cobalamin C defect"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8673-3181","authenticated-orcid":false,"given":"Giorgia","family":"Olivieri","sequence":"first","affiliation":[{"name":"Division of Metabolic Diseases and Hepatology Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Greco","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases and Hepatology Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Cairoli","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases and Hepatology Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Catesini","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases and Hepatology Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca Romana","family":"Lepri","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, Translational Cytogenomics Research Unity Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Orazi","sequence":"additional","affiliation":[{"name":"National Centre of Services and Research for the Prevention of Blindness and Rehabilitation of Visually Impaired, IAPB Italia Onlus  Rome Italy"},{"name":"Ophthalmology Unit Fondazione Policlinico Universitario A. Gemelli, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mallardi","sequence":"additional","affiliation":[{"name":"Clinical Psychology Unit Fondazione Policlinico Universitario A. Gemelli, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Martinelli","sequence":"additional","affiliation":[{"name":"Division of Metabolic Diseases and Hepatology Bambino Ges\u00f9 Children's Hospital, IRCCS  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Ricci","sequence":"additional","affiliation":[{"name":"National Centre of Services and Research for the Prevention of Blindness and Rehabilitation of Visually Impaired, IAPB Italia Onlus  Rome Italy"},{"name":"Pediatric Neurology Unit Fondazione Policlinico Universitario A. 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