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 beta-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 less than or equal to 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.

Neurodevelopmental and Cognitive Outcomes of Classical Homocystinuria: Experience from Qatar

“…Our study concurs with previous studies that reported similar or even higher rates of psychiatric/behavioural disorders among cases of homocystinuria (Abbott et al 1987). Another significant finding is that all those cases bar one had total IQs that are low average or below 70.…”

“…Another significant finding is that all those cases bar one had total IQs that are low average or below 70. The association between psychiatric/behavioural problems and low IQ in CHU has been reported previously (Abbott et al 1987). However, it is not clear from our study if those cases have behavioural/emotional issues secondary to their low cognitive abilities or they have primary behavioural/emotional problems that are independent of their IQ; particularly the parents have denied any formal diagnosis or follow-up of psychiatric illness among the cases.…”

Adherence Issues in Inherited Metabolic Disorders Treated by Low Natural Protein Diets

“…In addition, in PKU, low impulse control and mood variations [22] may hinder the ability to comply by reducing self-control and motivation to adhere to dietary restrictions. In conditions such as HCU [27] (mainly late diagnosed) and UCD, behavioural problems, such as aggression, episodic depression and personality disorders, add to health care professionals difficulties in being able to convince patients that the diet is essential. These difficulties are a particular issue during times of higher risk (e.g.…”

Homocistinuria, una enfermedad metabólica de diagnóstico tardío en el Perú.

“…Aquellos pacientes con homocistinuria que mantienen los valores adecuados de homocisteína (<11 μmol/L) desde temprana edad, antes de los 5 años, se relacionan con coeficientes intelectuales normales (18). El paciente presentó, además, alteraciones de comportamiento y psicosis, que suelen presentarse en la homocistinuria en más del 50% de pacientes adultos, que podrían ser secundarios al daño en la trasulfuración de la homocisteína que lleva a homocistinemia y hipermetioninemia por deficiencia marcada de la actividad de cistationina β-sintasa en el sistema nervioso central (19).…”