The enzyme hypoxanthine-guanine phosphoribosyl transferase (HPRT) catalyzes the reutilization of hypox­anthine and guanine to the purine nucleotides (nts) IMP and GMP, respectively. The HPRT deficiency is an X-linked recessive disorder characterized by uric acid over­production and variable neurological impairment. Virtu­ally complete deficiency of HPRT (activity less than 1.5%) is associated with the Lesch-Nyhan syndrome (LNS), whereas partial deficiency (residual activity at least 8.0%) is associated with the Kelley-Seegmiller syn­drome (KSS). The LNS is characterized by abnormal met­abolic and neurological manifestations and highly aggres­sive and destructive behavior, including a bizarre compul­sion towards self-mutilation. In contrast, KSS is usually associated only with the clinical manifestations of exces­sive purine production. After puberty, the hyperuricemia in KSS may cause gout. A third group of patients (with residual activity 1.5 to 8.0%) is associated with a neuro­logical variant of partial HPRT deficiency, with uric acid overproduction and neurological disability, that varies from minor clumsiness to debilitating extrapyramidal and pyramidal motor dysfunction [1].

Previous attempts to correlate different types or loca­tions of gene alterations to different phenotypes have been limited, not only by the relatively small numbers of avail­able cases, but probably also by the lack of an exact classi­fication of the clinical variants. The classification into four types enabled us to search for more precise correla­tion of described clinical variants with different types and locations of HPRT gene alterations.