CYP2D6 Genotype in Relation to Liver Toxicity Due to Tetrabenazine in Iraqi Patients with Hyperkinetic Movement Disorders

Abstract

The common types of movement disorders are; dystonia which is a syndrome of repetitive muscle contractions. While, Huntington disease is autosomal dominant progressive neurodegenerative disorder, which is characterized by involuntary movements (“chorea”).Tetrabenazine therapy has been shown to effectively control these movements compared to placebo. The most commonly reported side effects of tetrabenazine increase liver enzymes and these side effects are dose dependent.This is a prospective case controlled study was carried on 50 patients whom divided into 2 groups: group 1 involved 25 chorea patients, and group 2 included patients with dystonia, whom treated with (tetrabenazine) for three months. In addition to control group involved 25 healthy subjects to estimate the prevalence of genetic polymorphism of CYP 450 2D6 enzyme in related to tetrabenazine efficacy and toxicity. Blood samples were collected at the beginning to perform a genotyping assay for CYP 450 2D6 enzyme by PCR and to assess liver function and after three months of treatment to assess liver and measuring the plasma concentration of tetrabenazine , alpha and beta dihydrotetrabenazine by HPLC. The results show a significant CYP 450 2D6 enzyme polymorphism. And elevations of liver enzymes in the patient indicate hepatotoxicity of tetrabenazine and its metabolites.