{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:19:28Z","timestamp":1791285568093,"version":"4.1.0"},"reference-count":15,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[1997,6,1]],"date-time":"1997-06-01T00:00:00Z","timestamp":865123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[1997,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Among 40 patients with homocystinuria due to cystathionine \u03b2\u2010synthase deficiency diagnosed in the state of New South Wales, Australia (population 6 million) and followed long\u2010term, there were 10 deaths at ages 2\u201030 years. Of these 8 were definite vascular deaths, one was a presumed vascular death, and the other was due to an accident and unrelated to homocystinuria. The vascular deaths were all early cases and only one patient, a pyridoxine\u2010responsive 30\u2010year\u2010old woman, had been prescribed adequate treatment although it was uncertain that she was taking it.<\/jats:p><jats:p>In 32 patients of mean age 30 years (range 9\u201066 years) there were 539 patient\u2010years of treatment with pyridoxine, folic acid and hydroxocobalamin. There were 17 pyridoxine\u2010responsive patients and all maintained plasma total free homocyst(e)ine levels &lt;200\u00b5mol\/L over an average treatment period of 16.6 years. The 15 non\u2010responsive patients received additionally 6\u20109 g of betaine daily. This resulted in a further 74% mean decline (\u00b114% SD) in plasma total free homocyst(e)ine, persisting during an average (post\u2010betaine) treatment period of 11 years; current mean \u00b1 SD levels are 33 \u00b1 17 \u00b5mol\/L (n=15).<\/jats:p><jats:p>There were two vascular events during treatment, one fatal pulmonary embolus (see above) and one myocardial infarction, whereas without treatment, 21 would have been expected, \u03c72 = 14.22, p = 0.0001, relative risk 0.09 (95% CI 0.02\u20100.38). There were no events during 258 patient\u2010years of treatment in the 15 pyridoxine\u2010nonresponsive patients (p&lt;0.005 versus expected untreated). Nineteen patients had a total of 19 major and 15 minor operations requiring anaesthetic, and three had successful pregnancies, one whilst receiving betaine. There were no thromboembolic complications.<\/jats:p><jats:p>We conclude that treatment which effectively lowers circulating homocyst(e)ine, even to suboptimal levels, markedly reduces cardiovascular risk in patients with cystathionine \u03b2\u2010synthase deficiency, and that betaine therapy contributes importantly to this in pyridoxine\u2010nonresponsive patients. Betaine as additional therapy is safe and effective for at least 16 years.<\/jats:p>","DOI":"10.1023\/a:1005373209964","type":"journal-article","created":{"date-parts":[[2002,12,21]],"date-time":"2002-12-21T21:48:34Z","timestamp":1040507314000},"page":"295-300","source":"Crossref","is-referenced-by-count":171,"title":["The natural history of vascular disease in homocystinuria and the effects of treatment"],"prefix":"10.1002","volume":"20","author":[{"given":"D. E. L.","family":"Wilcken","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine University of New South Wales, The Prince Henry and Prince of Wales Hospitals  Sydney"},{"name":"Department of Cardiovascular Medicine, Clinical Sciences Building The Prince Henry Hospital  Little Bay Sydney 2036 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Wilcken","sequence":"additional","affiliation":[{"name":"The New Children's Hospital  Westmead, Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[1997,6]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1990.tb28064.x"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(93)90203-D"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199603213341204"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(95)00508-0"},{"key":"e_1_2_1_6_1","first-page":"17","article-title":"Nutritional ecogenetics: homocysteine\u2010related arteriosclerotic vascular disease, neural tube defects, and folic acid","volume":"58","author":"Motulsky AG","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_7_1","first-page":"1","article-title":"The natural history of homocystinuria due to cystathionine \u03b2\u2010synthase deficiency","volume":"37","author":"Mudd SH","year":"1985","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_8_1","first-page":"1279","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Mudd SH","year":"1995"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(81)80352-6"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116187"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118383"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000421520"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.48.1.58"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI108350"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198308253090802"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(98)90017-8"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1023%2FA%3A1005373209964","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1023\/A%3A1005373209964","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T02:59:03Z","timestamp":1694746743000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1023\/A%3A1005373209964"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,6]]},"references-count":15,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1997,6]]}},"alternative-id":["10.1023\/A:1005373209964"],"URL":"https:\/\/doi.org\/10.1023\/a:1005373209964","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,6]]}}}