Lesch-Nyhan disease and the basal ganglia

The purpose of this review is to summarize emerging evidence that the neuro behavioral features of Lesch-Nyhan disease (LND), a developmental disorder caused by congenital deficiency of the purine salvage enzyme hypoxanthine-g uanine phosphoribosyltransferase (HPRT), may be attributable to dysfunction of the basal ganglia. Affected individuals have severe motor disability de scribed by prominent extrapyramidal features that are characteristic of dys function of the motor circuits of the basal ganglia. They also display dist urbances of ocular motility, cognition, and behavioral control that may ref lect disruption of other circuits of the basal ganglia. Though neuropatholo gic studies of autopsy specimens have revealed no obvious neuroanatomical a bnormalities in LND, neurochemical studies have demonstrated 60-90% reducti ons in the dopamine content of the basal ganglia. In addition, recent PET s tudies have documented significant reductions in dopamine transporters and [F-18]fluorodopa uptake in the basal ganglia. These findings support the pr oposal that many of the neurobehavioral features of LND might be related to dysfunction of the basal ganglia. (C) 2000 Elsevier Science B.V. All right s reserved.