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

Abstract

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%, predominated 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 commom 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.