ABSTRACT
Lesch-Nyhan disease was first described in 1964 [1] as a syndrome in which disordered purine metabolism, as exemplified by hyperuricemia, uricaciduria, increased turnover of an enlarged uric acid pool and enormous overproduction of
purine de novo, was associated with a neurological picture resembling athetoid cerebral palsy and bizarre, compulsive, self-mutilative behavior. The overproduction of purine from an intravenous glycine precursor was 20 times the normal value [2], whereas in adults with gouty arthritis the largest rates observed were twice the normal value. The hallmark feature of the behavior was loss of tissue because of biting. The gene was recognized early from pedigree studies to be situated on the X chromosome [3], and transmission is as a fully recessive character. There have been a few affected females, most reflecting a nonrandom inactivation of the normal X chromosome. The enzyme defect in HPRT (Figure 65.1) was discovered in 1967 by Seegmiller, Rosenbloom and Kelley [4]. The gene was cloned in 1982 by Friedmann, Jolly and colleagues [5,6]. A large number of mutations have been defined [7].
