A 7-year-old boy is brought to the physician by his mother for a follow-up examination. He has had choreoathetosis, spasticity, and mental retardation since infancy and self-mutilation for 3 years. Laboratory studies show an increased serum uric acid concentration. The enzyme deficiency causing this disorder increases serum uric acid concentration by which of the following changes in purine metabolism?

Question

Quizplus · Accepted Answer

The symptoms and increased serum uric acid concentration are indicative of Lesch-Nyhan syndrome, which is caused by a deficiency in the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). This deficiency leads to decreased utilization of PRPP in the purine salvage pathway, resulting in increased de novo purine synthesis and subsequent overproduction of uric acid.  This patient is exhibiting symptoms of Lesch-Nyhan syndrome (LNS). Lesch-Nyhan syndrome is a disorder related to defects in the activity of the purine nucleotide salvage enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGPRT). The characteristic clinical features of the LNS are mental retardation, spastic cerebral palsy, choreoathetosis, uric acid urinary stones, and self-destructive biting of fingers and lips. The uric acid overproduction and its associated consequences (eg, gouty arthritis) are the result of a block in purine nucleotide salvage, leading to increased catabolism to uric acid resulting in hyperuricemia.

A 7-Year-Old Boy Is Brought to the Physician by His