Homocystinuria

Caused by cystathionine beta-synthase deficiency, which results in extreme elevations of plasma and urinary homocysteine levels

Autosomal recessive inheritance

Similar to Marfan syndrome in body habitus

Ectopia lentis almost always present

Mental impairment often present

Cardiovascular events caused by repeated arterial or venous thromboses

Bone mineral density is reduced in untreated patients

Life expectancy is reduced, especially in untreated and pyridoxine-unresponsive patients

Myocardial infarction, stroke, and pulmonary embolism are most common causes of death

Diagnosis suspected in patients in the second and third decades of life who have repeated arterial or venous thromboses and no other risk factors

DNA analysis can detect mutations in the cystathionine beta-synthase gene

Amino acid analysis of plasma is helpful diagnostic test: elevated plasma methionine and homocysteine levels

About 50% patients have a form of cystathionine beta-synthase deficiency that improves biochemically and clinically with pharmacologic doses of pyridoxine (50–500 mg/day) and folate (5–10 mg/day)

Treatment from infancy can prevent mental impairment and the other clinical problems

Patients who do not respond to pyridoxine must be treated with dietary reduction in methionine and supplementation of cysteine beginning in infancy

Vitamin betaine useful in reducing plasma methionine levels

Anticoagulation for documented venous thrombosis

Prophylactic use of warfarin or antiplatelet agents not recommended