HGPRT-Deficiency — The Molecular Basis of the Clinical Syndromes

Abstract

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is a purine salvage enzyme that plays a key role in the regulation of purine metabolism in man. Interest in this X-linked enzyme stems, in part, from the existence of two clinical syndromes associated with deficiency of HGPRT enzyme activity. In 1967, Seegmiller et al. [1] described a virtually complete deficiency of HGPRT activity in patients with the Lesch-Nyhan syndrome. This syndrome is characterized by an overproduction of uric acid as well as a bizarre constellation of neurologic and behavioral abnormalities, including mental retardation, spasticity, choreoathetosis, and a compulsive form of selfmultilation. A partial deficiency of HGPRT was subsequently demonstrated in several male patients who presented with hyperuricemia and a severe form of gout at an early age [2]. This latter group of patients is usually free of the central nervous system manifestations that characterize the Lesch-Nyhan syndrome, although an occasional patient with partial HGPRT deficiency and gout may exhibit minor neurologic manifestations, such as dysarthria, hyperreflexia, positive Babinski’s signs, or abnormalities of spinocerebellar function [3].