Homocystinuria

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Abstract
Homocystinuria, a recently described inborn error of methionine metabolism, resembles Marfan''s syndrome in its clinical manifestations, which include skeletal deformities, dislocation of eye lenses, and cardiovascular changes. However, homocystinuria is further characterized by a variable degree of mental defect and hypercoagulability of the blood; the latter may lead to thromboembolic accidents. Homocystinuria appears to be a recessive condition, whereas Marfan''s syndrome is usually inherited as a dominant trait. The basic metabolic error is thought to be a deficiency of cystathionine synthetase. Eight children with homocystinuria in 3 unrelated families have so far been diagnosed in British Columbia, Canada. In 3 of 7 untreated cases there is evidence of cerebral vascular thromboses having occurred during infancy, beginning at the ages of 5 to 9 mo. One boy died of bilateral renal vein thrombosis at -10 1/2 mo., and autopsy showed both old and recent cerebral infarcts due to multiple venous thromboses. The children who survived their cerebrovascular accidents are prone to seizures and present neurological and electroencephalographic abnormalities. One of our patients without seizures has normal intelligence at the age of 17 yr. Infants with homocystinuria appear entirely normal at birth, before the characteristic clinical picture develops. The early diagnosis depends on urine tests. The possibility of homocystinuria should be remembered in children with "acute infantile hemiplegia" or any stroke or severe motor seizures and as a differential diagnosis of encephalitis and cerebral thrombophlebitis. Later, homocystinuria should be suspected in patients with ectopia lentis or Marfan''s syndrome who, in addition, are mentally defective or have no history of a similar condition in previous generations. Preliminary attempts to devise methionine and homocystine loading tests which would detect the carrier state for the gene producing homocystinuria are described. The administration of a low-protein diet to one homocystinuric child was shown to be effective in decreasing the serum concentration and urinary excretion of methionine and homocystine. The mental deficiency, ectopia lentis, and skeletal defects of homocystinuria, and particularly the intravascular thromboses and their serious consequences, may possibly be prevented by the early institution of a low-methionine diet, supplemented with cystine. This possibility is now being explored in a newborn homocystinuric infant. Since early diagnosis is essential, we recommend the routine use of a simple cyanide-nitroprusside screening test on the urines of all newborn infants.