Animal Models for Lesch-Nyhan Disease

In 1964, in the Johns Hopkins clinics, Michael Lesch and William Nyhan saw two brothers with cerebral palsy, movement disorder, and an extremely high plasma uric acid (VA) level. Most striking in these patients was compulsive self-mutilatory behavior (SMB) involving intense biting of the digits and lips. Careful metabolic study showed profound hyperuricemia and hyperuricosuria in this syndrome, now known as Lesch-Nyhan disease (LND). When adjusted for body wt, total daily UA excretion was often 100 times normal (Nyhan et al., 1965 ). Because of the unusual association of hyperuricemia and a behavioral abnormality, other cases were quickly identified, and an X-linked recessive pattern of inheritance was deduced. In 1967, J. E. Seegmiller and his colleagues reported that erythrocytes from patients with LND possessed less than 0.001% of normal activity for the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT).