Purine Salvage and Lesch-Nyhan Syndrome

Key points

• • HGPRT (hypoxanthine-guanine phosphoribosyltransferase) salvages hypoxanthine to IMP and guanine to GMP, consuming PRPP.
• • Complete HGPRT deficiency is Lesch-Nyhan syndrome and is inherited in an X-linked recessive pattern.
• • Without salvage, PRPP accumulates and drives de novo purine synthesis, so more purine is degraded to uric acid, causing hyperuricaemia and orange urate crystals in the nappy.
• • The neurological picture is dystonia, choreoathetosis, developmental delay and characteristic compulsive self-mutilation of lips and fingers.
• • Partial HGPRT deficiency (Kelley-Seegmiller syndrome) causes hyperuricaemia and gout without the severe neurological features.