Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is a hereditary disorder of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of the enzyme deficiency.

Epidemiology

Prevalence of HPRT deficiency is unknown but estimated prevalence for Lesch-Nyhan syndrome (LNS; see this term) is estimated between 1/380,000 and 1/235,000 live births. Males are generally affected and heterozygous females are carriers (usually asymptomatic).

Clinical description

Onset occurs during infancy. Two forms of the disease have been described: LNS, the most severe form, with a complete enzyme deficiency, and Lesch-Nyhan variants with partial HPRT deficiency. LNS is characterized by uric acid overproduction-related symptoms associated with urolithiasis and gout, severe neurological manifestations, hematological disturbances, and compulsive self-injurious behaviour. LNS patients have a limited life expectancy. In the less severely affected LNS variants, also termed Kelley-Seegmiller syndrome (KSS; see this term), uric acid overproduction-related symptoms are prominent, neurological manifestations are usually unapparent, compulsive self-injurious behaviour is absent and patients have a normal life expectancy.

Etiology

Inheritance is X-linked recessive and HPRT deficiency results from mutations in the HPRT1 gene (Xq26).