This is a rare, X-linked, recessive disorder caused by deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT); degree of deficiency (and hence manifestations) vary with the specific mutation. HPRT deficiency results in failure of the salvage pathway for hypoxanthine and guanine. These purines are instead degraded to uric acid. Additionally, a decrease in inositol monophosphate and guanosyl monophosphate leads to an increase in conversion of 5-phosphoribosyl-1-pyrophosphate (PRPP) to 5-phosphoribosylamine, which further exacerbates uric acid overproduction. Hyperuricemia predisposes to gout and its complications. Patients also have a number of cognitive and behavioral dysfunctions, etiology of which is unclear; they do not appear related to uric acid.
Diagnosis is suggested by the combination of dystonia, retardation, and self-mutilation. Serum uric acid levels are usually elevated, but confirmation by HPRT enzyme assay is usually done.
CNS dysfunction has no known treatment; management is supportive. Self-mutilation may require physical restraint, dental extraction, and sometimes drug therapy; a variety of agents has been used. Hyperuricemia is treated with a low-purine diet (eg, avoiding organ meats, beans, sardines) and allopurinol Some Trade Names ZYLOPRIM Click for Drug Monograph , a xanthine oxidase inhibitor (the last enzyme in the purine catabolic pathway). Allopurinol Some Trade Names ZYLOPRIM Click for Drug Monograph prevents conversion of accumulated hypoxanthine to uric acid; because hypoxanthine is highly soluble, it is excreted.