Homocystinuria is a rare autosomal recessive inherited metabolic disorder caused by a defect in an enzyme that converts homocysteine to cystathione. Cystathionine beta synthase results in accumulation of homocysteine in the blood and its excretion in urine.
The clinical manifestations of homocystinuria include developmental delay/intellectual disability, ectopia lentis and/or severe myopia, skeletal abnormalities (excessive height and length of the limbs), thromboembolism and severe premature atherosclerosis.
Less marked rises in the plasmatic homocysteine are much more frequent and are present in about 5- 7% of the population. Although it is not associated with the clinical stigmas of homocystinuria, growing evidence suggests that moderate hyperhomocysteinemia is an independent risk factor for vascular atherosclerosis and recurrent venous thromboembolism.
Higher concentration levels of plasmatic homocysteine can occur due to genetic defects in the enzymes implicated in homocysteine metabolism, nutritional deficiencies in vitamin cofactors or with other factors including some chronic and medicinal medical conditions. Some medicines used in hypercholesterolemia such as fibrates and nicotinic acid can elevate homocysteine levels in approximately a 30%; however the clinical significance of this is uncertain. Smoking can also raise the levels of homocysteine and chronic renal insufficiency owing to the decrease in renal elimination and metabolic disorders caused.
This is the most frequent of the methionine metabolisms. Neonatal screening is carried out world-wide with a prevalence of cases between 1 in 200,000 and 1 in 350,000. The disorder appears to be more frequent in New South Wales (Australia) (1 in 60,000) and Ireland. Early treatment of patients identified by screening programs has produced favorable results.
Homocystinuria is an inherited autosomal recessive disorder. The cystathionine beta synthase gene is located on the chromosome 21q22.3 and the majority of the patients are heterozygous for the two different alleles. The heterozygous carriers are usually asymptomatic; thromboembolism and cardiomyopathy are more frequent in this group than in the general population.