Lesch–Nyhan Disease

Abstract

Lesch-Nyhan disease (LND) is an X-linked inherited disorder caused by deficiency of the purine salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HPRT). Patients with severe enzyme deficiency exhibit a characteristic neurobehavioral syndrome along with evidence for systemic overproduction of uric acid. The neurobehavioral syndrome includes severely disabling generalized dystonia, mild-moderate cognitive impairment, impulsive and aggressive behaviors, and uncontrollable self-injury. The overproduction of uric acid leads to hyperuricemia, hyperuricosuria, uric acid kidney stones, early gouty arthritis, and rarely subcutaneous tophi. Patients with partial enzyme deficiency also overproduce uric acid but exhibit variable expression of the neurobehavioral syndrome. Some variants exhibit no detectable neurobehavioral defects or only mild subclinical clumsiness, while others have severe generalized dystonia and cognitive impairment but no behavioral manifestations.