Acute Renal Failure During Adenine Therapy in Lesch-Nyhan Syndrome

  • Mario Ceccarelli
  • Maria Laura Ciompi
  • Giampiero Pasero
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 41)


Additional adenine and folic acid are required for optimal growth of hypoxanthine-guaine phosphoribosyltransferase (HGPRT) deficient fibroblasts in tissue culture(1). On this ground adenine therapy was advised in Lesch-Nyhan (LN) syndrome and resulted in a prompt correction of megaloblastic anemia in two cases(2). In mammalian tissue adenine is easily converted into adenosine monophosphat by adenine phosphoribosyltransferase, utilizing 5-phosphoribosylpyrophosphate (PRPP). “Inappropriate” purine biosynthesis “de novo” in ln syndrome can be just accounted for an increased availability of PRPP due to missing competition between HGPRT and glutamine-PRPP-amidotransferase for this substrate(3–5). Consequently PRPP consumption from adenine is likely to result in a decreased purine biosynthesis, as proved by lesser incorporation of 14C-glycine in urinary uric acid (ua)(2). Nevertheless adenine therapy showed conflicting evidence of inhibiting purine biosynthesis, since a decrease of urinary ua was not evidenced in two cases in spite of a reduction of erythrocyte PRPP(6). Therefore we think that any further contribution on this topic is of some interest.


Megaloblastic Anemia Spastic Cerebral Palsy Amniotic Fluid Cell Purine Biosynthesis Urinary Uric Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. (1).
    De Mars R., Sarto G., Felix J.S. Benke P.: Lesch-Nyhan mutation: prenatal detection with amniotic fluid cells. Science 164, 1303, 1969.CrossRefGoogle Scholar
  2. (2).
    Van der Zee S.P.M., Lommen E.J.P., Trubels J.M.F., Schretlen E.D.A.M.: The influece of adenine on the clinical features and purine metabolism in the Lesch-Nyhan syndrome. Acta Paediat. Scand. 59, 259, 1970.CrossRefGoogle Scholar
  3. (3).
    Rosenbloom F.M., Henderson J.F., Caldwell I.C., Kelley W.N., Seegmiller J.E.: Biochemical bases of accelerated purine biosynthesis “de novo” in human fibroblasts lacking hypoxanthine-guanine phosphoribosyl-transferase. J.Biol.Chem. 243, 1166, 1968.PubMedGoogle Scholar
  4. (4).
    Greene M.L., Seegmiller J.E.: Elevated erythrocyte phosphoribosylpyrophosphate in X-linked uric aciduria: importance of PRPP concentration in the regulation of human purine biosynthesis. J.Clin.Invest. 48, 32a, 1969.Google Scholar
  5. (5).
    Pasero G., Ciompi M.L.: L’importanza del fosforibosil-pirofosfato (PRPP) nella biosintesi purinica. Atti Simposio int. su Malattie reumatiche e alterazioni metaboliche. (to be published).Google Scholar
  6. (6).
    Schulman J.D., Greene M.L., Fujimoto W.Y., Seegmiller J.E.: Adenine therapy for Lesch-Nyhan syndrome. Pediat. Res. 5, 77, 1971.CrossRefGoogle Scholar
  7. (7).
    Nissim S., Ciompi M.L., Barzan L., Pasero G.: Coreo-atetosi, insufficienza mentale, automutilazione, alterazioni del metabolismo purinico: la sindrome di Lesch-Nyhan. Prima osservazione in Italia. Neuropsich. Infant. 135, 709, 1972.Google Scholar
  8. (8).
    Ceccarelli M., Ciompi M.L., Taddeucci G., Pasero G.: Nuova osservazione di sindrome di Lesch-Nyhan. Reumatismo (to be published).Google Scholar
  9. (9).
    Bendich A., Brown G.B., Philips F.S., Thiersch J.B.: Direct oxidation of adenine “in vivo”. J.Biol.Chem. 183, 267, 1950.Google Scholar
  10. (10).
    Philips F.S., Thiersch J.B., Bendich A.: Adenine intoxication in relation to “in vivo” formation and deposition of 2,8-dioxyadenine in renal tubules. J.Pharmacol. 104, 20, 1952.Google Scholar

Copyright information

© Springer Science+Business Media New York 1974

Authors and Affiliations

  • Mario Ceccarelli
    • 1
  • Maria Laura Ciompi
    • 1
  • Giampiero Pasero
    • 1
  1. 1.Deptm. of Pediatrics and Deptm. of Internal MedicineUniversity of PisaItaly

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