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Classical homocystinuria: Vascular risk and its prevention
Author(s) -
Yap S.
Publication year - 2003
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1023/a:1024497419821
Subject(s) - homocystinuria , medicine , cystathionine beta synthase , homocysteine , pediatrics , vascular disease , surgery , methionine , biochemistry , chemistry , amino acid
Summary. Homocystinuria due to cystathionine β‐synthase deficiency is the second most treatable aminoacidopathy. The reported incidence varies from 1 in 344 000 worldwide to 1 in 65 000 in Ireland. Untreated patients with homocystinuria have severe hyperhomocysteinaemia. Amongst its pathological sequelae, which include mental retardation, ectopia lentis and osteoporosis, vascular events remain the major cause of morbidity and mortality in untreated patients. Recognized modalities of treatment include pyridoxine, in combination with folic acid and vitamin B 12 ; methionine‐restricted, cystine‐supplemented diet; and betaine. The natural history of vascular events is such that half will have an event before age 30 years and there is a predicted one event per 25 years at the time of maximal risk. In 158 patients with 2822 patient‐years of treatment, there would be a predicted 112 events if left untreated, but instead only 17 vascular events were recorded during treatment (relative risk 0.09, 95% CI 0.036 to 0.228; p <0.0001). Appropriate chronic treatment to lower hyperhomocysteinaemia is effective in reducing the potentially life‐threatening vascular risk in patients with homocystinuria. These findings may also have relevance to the significance of mild hyperhomocysteinaemia that is commonly found in patients with premature vascular disease.