Gilles de la Tourette's syndrome: biochemical approaches

Abstract

Haloperidol, a dopamine receptor blocking agent, is the most effective therapy for Tourette's syndrome. In five patients with Tourette's syndrome, we found in the CSF an elevated probenecid-induced accumulation of HVA, the major metabolite of dopamine. This supports the hypothesis that Tourette symptoms are related to an increased firing of dopaminergic neurons in the central nervous system; haloperidol relieves these symptoms by blocking dopamine receptors. Some similarities of Tourette's syndrome to Lesch-Nyhan's syndrome prompted us to compare these two disorders, obtaining data from a large number of Tourette patients. In a questionnaire completed by 114 patients with Tourette's syndrome, the incidence of self-destructive behavior was 43%, a family history of gout or hyperuricemia was present in 27%, and 11% had a family history of Tourette's syndrome or tics. We propose that Tourette's syndrome could be a genetic disorder of purine metabolism which may result in neurotransmitter abnormalities such as an increased brain dopamine turnover.