Homocystinuria

Pathophysiology

1) group of seven different disorders 2) most common variant is caused by deficiency in cystathionine-beta-synthase 3) thought to involve abnormal cross-linking of collagen, fibrillin, and macromolecules

Signs and Symptoms

1) mental retardation/psychiatric problems 2) tall stature 3) skeletal defects (osteoporosis) 4) retinal detachment 5) increased thromboses 6) lens dislocation (downward and medially) 7) severe atherosclerosis

Characteristic Test Findings

Laboratory – 1) increased serum homocystine 2) increased urine homocytine 3) increased serum methionine in some variants 4) positive cyanide-nitroprusside test

Associated Conditions

1) myocardial infarction 2) pulmonary embolus 3) cerebral vascular accidents 4) deep venous thrombosis 5) peripheral artery disease 6) vision loss and glaucoma

Biochemistry

second most common variant has defect in methionine synthase

Treatment

1) early pyridoxine (induces cystathionine beta synthase activity) to blunt development of sequelae 2) low protein diet to methionine intake 3) maintenance of physiologic levels of cofactors folate, vitamin B6, and vitamin B12

Tips for USMLE

1) clinical features can be confused with Marfan’s disease 2) best way to differentiate is the mental retardation that occurs in homocystinuria but not Marfan’s 3) the lens subluxation in Marfan’s is upward and outward; in homocystinuria, it is downward and inward