Neurocognitive functioning in Lesch-Nyhan disease and partial hypoxanthine-guanine phosphoribosyltransferase deficiency

Lesch-Nyhan disease (LND) is a rare, X-linked genetic disorder that involve s the nearly complete absence of an enzyme (hypoxanthine-guanine phosphorib osyltransferase, or HPRT) that is essential for purine salvage. In addition to hyperuricemia, all patients with classic LND suffer from movement disor der and compulsive self-injury, and most have mental retardation. Patients with partial HPRT deficiency (variants) always have hyperuricemia and often have neurologic abnormalities, but do not self-injure and usually are desc ribed as having normal intelligence. Here we compare 15 patients with LND t o 9 variants and 13 normal adolescents and adults. Testing revealed unambig uous and qualitatively similar cognitive deficits in both patient groups. T he variants produced scores that were intermediate between those of patient s with LND and normal participants on nearly every cognitive measure. We di scuss these findings in terms of what is known about the neuropathology of LND.