A genetic lack of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity, seen almost exclusively in young boys, results in a bizarre set of symptoms called Lesch-Nyhan syndrome.
B.
Children with this genetic disorder, which becomes manifest by the age of 2 years, are sometimes poorly coordinated and have intellectual deficits. In addition, they are extremely hostile and show compulsive self-destructive tendencies: they mutilate themselves by biting off their fingers, toes, and lips.
C.
The devastating effects of Lesch-Nyhan syndrome illustrate the importance of the salvage pathways. Hypoxanthine and guanine arise constantly from the breakdown of nucleic acids. In the absence of HGPRT , PRPP levels rise and purines are overproduced by the de novo pathway, resulting in high levels of uric acid production and goutlike damage to tissue.
D.
The brain is especially dependent on the salvage pathways, and this may account for the central nervous system damage in children with Lesch-Nyhan syndrome. This syndrome is another potential target for gene therapy.