Female carriers of the X-linked recessive disorder hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency show somatic cell mosaicism, and this may cause an increased synthesis of purines. We have examined whether urinary oxypurines could be useful for carrier diagnosis.Methods
Carrier testing was performed in 35 women belonging to 16 unrelated Spanish families with at least one subject affected by the Lesch-Nyhan syndrome (11 families, 14 patients) or the Kelley-Seegmiller syndrome (five families, six patients) by means of HPRT and adenine phosphoribosyltransferase activities in hair follicles and/or molecular studies. Plasma and 24-h urinary concentrations of hypoxanthine, xanthine and uric acid were measured while subjects were on a purine-restricted diet.Results
Mean plasma urate concentrations and 24-h urinary hypoxanthine, xanthine and uric acid excretion rates were significantly higher in 22 heterozygotes than in 13 non-carriers (P < 0.02). Daily urinary oxypurine excretion rates were also significantly higher in heterozygotes than in 12 normal women (P = 0.0011). Cumulative 5-day radioactivity excretion after [8-14C]-adenine infusion was markedly increased in 10 carrier women compared with five normal women (P = 0.0369). The sensitivity of 24-h urinary hypoxanthine and xanthine excretion rates was 86% and 77%, respectively, and the specificity 100% for both tests.Conclusion
Female heterozygotes for HPRT deficiency show an enhanced purine nucleotide degradation and purine overproduction. An elevated hypoxanthine and/or xanthine excretion rate differentiated most heterozygotes for HPRT deficiency from non-carrier women and thus could be useful for carrier diagnosis.