{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T01:42:27Z","timestamp":1792978947122,"version":"4.5.0"},"reference-count":29,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T00:00:00Z","timestamp":1736726400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["NU23\u201007\u201000383"],"award-info":[{"award-number":["NU23\u201007\u201000383"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016366","name":"V\u0161eobecn\u00e1 Fakultn\u00ed Nemocnice v Praze","doi-asserted-by":"publisher","award":["RVO\u2010VFN64165"],"award-info":[{"award-number":["RVO\u2010VFN64165"]}],"id":[{"id":"10.13039\/501100016366","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007397","name":"Univerzita Karlova v Praze","doi-asserted-by":"publisher","award":["Cooperatio\u2010MetabolicDisorders"],"award-info":[{"award-number":["Cooperatio\u2010MetabolicDisorders"]}],"id":[{"id":"10.13039\/100007397","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":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Cystathionine \u03b2\u2010synthase (CBS) deficiency (classical homocystinuria) has a wide range of severity. Mildly affected patients typically present as adults with thromboembolism and respond to treatment with pyridoxine. Severely affected patients usually present during childhood with learning difficulties, ectopia lentis and skeletal abnormalities; they are pyridoxine non\u2010responders (NR) or partial responders (PR) and require treatment with a low\u2010methionine diet and\/or betaine. The European network and registry for Homocystinurias and methylation Defects (E\u2010HOD) has published management guidelines for CBS deficiency and recommended keeping plasma total homocysteine (tHcy) concentrations below 100\u2009\u03bcmol\/L. We have now analysed data from 311 patients in the registry to see how closely treatment follows the guidelines. Pyridoxine\u2010responsive patients generally achieved tHcy concentrations below 50\u2009\u03bcmol\/L, but many NRs and PRs had a mean tHcy considerably above 100\u2009\u03bcmol\/L. Most NRs were managed with betaine and a special diet. This usually involved severe protein restriction and a methionine\u2010free amino acid mixture, but some patients had a natural protein intake substantially above the WHO safe minimum. Work is needed on the methionine content of dietary protein as estimates vary widely. Contrary to the guidelines, most NRs were on pyridoxine, sometimes at dangerously high doses. tHcy concentrations were similar in groups prescribed high or low betaine doses and natural protein intakes. High tHcy levels were probably often due to poor compliance. Comparing time\u2010to\u2010event graphs for NR patients detected by newborn screening and those ascertained clinically showed that treatment could prevent thromboembolism (risk ratio 0.073) and lens dislocation (risk ratio 0.069).<\/jats:p>","DOI":"10.1002\/jimd.12844","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T01:36:14Z","timestamp":1736818574000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cystathionine \u03b2\u2010Synthase Deficiency in the E\u2010<scp>HOD<\/scp> Registry\u2014Part <scp>II<\/scp>: Dietary and Pharmacological Treatment"],"prefix":"10.1002","volume":"48","author":[{"given":"Andrew A. 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