Homocystinuria due to cystathionine β-synthase deficiency: Clinical manifestations and therapy

Deficiency of cystathionine β-synthase activity causes diverse clinical manifestations, most or all of which probably result from slowly progressive toxic effects of homocysteine and its metabolites. In about one half of these patients, ingestion of pharmacologic amounts of pyridoxine (50-1000 mg/day) ameliorates or completely corrects the biochemical abnormalities. The pyridoxine non-responding patients potentially benefit either from a methionine-restricted diet, which also will correct the biochemical abnormalities, or from various anti-platelet agents which may at least decrease the likelihood of thromboembolic complications. Since the disorder is progressive and since therapy is available, early diagnosis is important. Early diagnosis requires physician awareness of the protean manifestations of cystathionine β-synthase deficiency and use of plasma amino acid measurements or the cyanide-nitroprusside test of urine to screen for affected individuals. Some states now include a test for hypermethioninemia in their neonatal screening programs. A case report ilustrates the varied clinical problems of these patients and the efficacy of pyridoxine and dietary therapy in this disorder.