Classic homocystinuria: etiology, natural history and treatment

Abstract

Classic homocystinuria is a rare autosomal recessive disorder of methionine metabolism resulting from a deificiency of cystathionine beta-synthase that is involved in transsulfuration of homocysteine. The disorder is caused by mutations of CBS gene. Lack of enzyme is associated with accumulation of homocysteine that induce various toxicities, e.g. endothelial dysfunction and increased risk of thrombosis. Clinical manifestations of classic homocystinuria include ectopia lentis and/or severe myopia, skeletal abnormalities (marfanoid habitus, generalized osteoporosis and bone deformity), mental retardation, seizures, psychiatric and behavioral disorderts, venous and arterial thrombosis. Some patients with milder form of the disease can present only with thromboembolic events in adulthood. Diagnosis of classic homocystinuria should by established by biochemical (elevated plasma homocysteine and methionine and low cistathione) and genetic (homozygous and compound heterozygous mutations of CBS gene) tests. Low methionine diet, vitamin B6, folic acid and betaine anhydrous, a methylating agent, can be used to reduce homocysteine levels, to prevent progression of the homocystinuria and thromboembolic events.