Purine Metabolism in Female Heterozygotes for Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency

Eur J Clin Invest. 1998 Nov;28(11):950-7. doi: 10.1046/j.1365-2362.1998.00392.x.


Background: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Female
  • Heterozygote*
  • Humans
  • Hypoxanthine / urine
  • Hypoxanthine Phosphoribosyltransferase / deficiency*
  • Hypoxanthine Phosphoribosyltransferase / genetics*
  • Lesch-Nyhan Syndrome / enzymology
  • Lesch-Nyhan Syndrome / genetics*
  • Lesch-Nyhan Syndrome / metabolism*
  • Male
  • Middle Aged
  • Purines / metabolism*
  • Spain
  • Xanthine / urine


  • Purines
  • Xanthine
  • Hypoxanthine
  • Hypoxanthine Phosphoribosyltransferase