[2,8-dihydroxyadenine nephrolithiasis: from diagnosis to therapy]

Ann Biol Clin (Paris). Nov-Dec 2007;65(6):585-92.
[Article in French]

Abstract

Adenine phosphoribosyltransferase (APRT, EC 2.4.2.7) deficiency is an enzymopathy of purine metabolism, which is inherited as an autosomal recessive trait. APRT is a salvage enzyme that normally catalyzes the conversion of adenine to adenosine monophosphate. APRT deficiency results in adenine accumulation with oxidation by xanthine dehydrogenase (XDH; EC 1.1.1.204) to 2,8-dihydroxyadenine (2,8-DHA) then excreted in urine. This compound is extremely insoluble and its crystallization can lead to stone formation and renal failure. The diagnosis of the disease is based on stone analysis by infrared spectroscopy or microscopic examination of urine, which may reveal typical 2,8-DHA crystals. The enzyme activity measurements in erythrocyte lysates will identify both homozygotes and heterozygotes for APRT deficiency. Molecular approach can identify mutations which are responsible of this inherited disease. Two types of deficit are commonly distinguished, depending on the level of residual APRT activity: type I, mainly observed in Caucasian subjects, in whom the enzyme activity is undetectable in homozygous patients and type II, found in Japanese patients who are able to form APRT but the enzyme activity is strikingly reduced because a low affinity for phosphoribosylpyrophosphate. The crystallization of 2,8-DHA and subsequent renal damages may be prevented with allopurinol therapy, a xanthine oxidase inhibitor. The role of the laboratory is crucial to detect APRT deficiency and to assess the efficacy of therapy, the objective being to avoid 2,8-DHA crystal formation.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine Phosphoribosyltransferase / deficiency*
  • Humans
  • Kidney Calculi / chemically induced
  • Kidney Calculi / enzymology
  • Nephrolithiasis / complications
  • Nephrolithiasis / diagnosis*
  • Nephrolithiasis / epidemiology
  • Nephrolithiasis / physiopathology
  • Renal Insufficiency / epidemiology

Substances

  • 2,8-dihydroxyadenine
  • Adenine Phosphoribosyltransferase
  • Adenine