Psychiatric manifestations of homocystinuria due to cystathionine β-synthase deficiency: Prevalence, natural history, and relationship to neurologic impairment and vitamin B₆-responsiveness

Homocystinuria commonly affects the central nervous system (CNS), primarily as mental retardation, seizures, and stroke. Case reports have long suggested a predisposition to schizophrenia, but no careful study of predisposition to psychiatric illness has been performed. Accordingly, we evaluated 63 persons with homocystinuria due to cystathionine β-synthase deficiency for psychiatric disturbance, intelligence, evidence of other CNS problems, and responsiveness to vitamin B₆. The overall rate of clinically significant psychiatric disorders was 51%, predominantly by four diagnostic categories: episodic depression (10%), chronic disorders of behavior (17%), chronic obsessive-compulsive disorder (5%), and personality disorders (19%). The average IQ was 80 ± 27 (1 SD); and an IQ of ≤79 was two-thirds more common among vitamin B₆-nonresponsive patients compared to vitamin B₆-responsive patients. Aggressive behavior and other disorders of conduct were particularly common among patients with mental retardation and among vitamin B₆-nonresponsive patients.