Question:

A 4-year-old boy has delayed motor development and choreoathetosis. He had normal
development at birth. He chews his fingers and lips, which has resulted in tissue loss. He has arthritis. Serum and urine uric acid concentrations are increased. Which of the following abnormalities is the most likely cause of these findings?

Correct Answer: B.  Hypoxanthine-guanine phosphoribosyltransferase deficiency

Self-mutilation is a classic symptom of Lesch-Nyhan syndrome, a genetic HPRT enzyme deficiency. Purines, namely guanine and hypoxanthine, are recycled to GMP and IMP by HPRT (Answer D). A deficiency in HPRT (Answer B) forces purines to be degraded to excess uric acid. Another purine salvage pathway deficiency, APRT deficiency (Answer A), leads to toxic buildup of adenosine metabolites in B and T cells, one of the causes of SCID. Answer C describes nucleic acid recycling, which should prevent uric acid accumulation. PRPP (Answer E) is a purine synthesis enzyme; PRPP superactivity, not deficiency, would cause uric acid buildup.