Homocystinuria

Key Features

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

• Autosomal recessive inheritance

Clinical Findings

• 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

• 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

Treatment

• 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