Five boys with Lesch-Nyhan syndrome and varying degrees of dystonia, chorea, spasticity, ataxia, dysarthria, and mental retardation were studied at the Depts of Neurology and Medicine, Baylor College of Medicine, and Depts of Neurology and Pediatrics, University of Texas Health Science Center, Houston, TX. Four showed reduction of homovanillic acid (HVA) in the CSF and all had low CSF phenethylene glycol, indicating reducee dopamine and norepinephrine turnover. Three children had high CSF 5-hydroxyindoleacetic acid (HIAA), suggesting increased serotonin turnover. The patient with the most severe chorea had the lowest CSF HVA value, whereas the patient with the least amount of self-mutilation had the highest CSF 5HIAA. Only one patient improved with carbidopa-levodopa, whereas all 5 showed some lessening of self-mutilatory or hyperkinetic behavior in response to tetrabenazine, a monoamine-depleting agent. The study was thought to support the theory of abnormal central monoamine metabolism in Lesch-Nyhan syndrome. [1]

COMMENT: Lesch-Nyhan syndrome is an X-linked recessive disorder of purine metabolism characterized by hypotonia followed by spasticity, chorea, athetosis, dystonia, growth and mental retardation, self-mutilatory behavior, hyperuricemia, and nephrolithiasis [2]. The phenotypical expression is the result of a deficiency of hypoxanthineguanine phosphoribosyl-transferase enzyme, the gene located on the long arm of the X chromosome. Response to medications is variable but self-mutilation can sometimes be ameliorated. [3]