Diagnosis of Genotypes for Adenine Phosphoribosyltransferase (APRT) Deficiency

  • Naoyuki Kamatani
  • Shoko Kuroshima
  • Chihiro Terai
  • Masayuki Hakoda
  • Kusuki Nishioka
  • Kiyonobu Mikanagi
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 253A)


Adenine phosphoribosyltransferase (APRT) deficiency is a cause of urolithiasis and renal failure (1, 2). Due to the deficiency of APRT, adenine cannot be converted to AMP, and adenine thus accumulated in the body is catabolized to 2, 8-dihydroxyadenine via xanthine oxidase. Since 2, 8-dihydroxyadenine is a quite insoluble material, it makes crystals in urine. Although mild cases develop urinary stones (3), renal failure requiring hemodialysis or renal transplantation could occur in severe cases (4, 5). Since this disease can successfully be treated with allopurinol, correct diagnosis is important (2).


Mutant Allele Xanthine Oxidase Urinary Stone Mutant Enzyme Normal Enzyme Activity 
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  1. 1.
    P. Cartier, and M. Hamet, Une nouvelle maladie metabolique: le deficit complete en adenine-phosphoribosyltransferase avec lithiase de 2, 8-dihydroxyadenine., C. R. Acad. Sci. (Paris) 279: 883 (1974).Google Scholar
  2. 2.
    H. A. Simmonds and K. J. Van Acker, Adenine phosphoribosyltransferase deficiency: 2, 8-dihydroxyadenine lithiasis., in: “The Metabolic Basis of Inherited Disease,” J. B. Stanbury, J. B. Wyngaarden, D. S. Fredrickson, J. L. Goldstein, M. S. Brown eds., MaGraw-Hill Book Company, New York, p 1144 (1983).Google Scholar
  3. 3.
    F. R. Witten, J. W. Morgan, J. G. Foster, and J. F. Glenn, dihydroxyadenine urolithiasis: Review of the literature and report of a case in the United States., J. Urol. 130: 938 (1983).PubMedGoogle Scholar
  4. 4.
    M. C. Greenwood, M. J. Dillon, H. A. Simmonds, T. C. M. Barratt, J. R. Pinocott, and C. Metreweli, Renal failure due to 2, 8-dihydroxyadenine urolithiasis., Eur. J. Pediatr. 138: 346 (1982).PubMedCrossRefGoogle Scholar
  5. 5.
    K. J. Van Acker, H. A. Simmonds, C. Potter, and J. S. Cameron, Complete deficiency of adenine phosphoribosyltransferase: report of a family., N. Engl. J. Med. 297: 127 (1977).PubMedCrossRefGoogle Scholar
  6. 6.
    N. Kamatani, C. Terai, S. Kuroshima, K. Nishioka, and K. Mikanagi, Genetic and clinical studies on 19 families with adenine phosphoribosyltransferase deficiencies., Hum. Genet. 75: 163 (1987).PubMedCrossRefGoogle Scholar
  7. 7.
    N. Kamatani, T. Sonoda, and K. Nishioka, Distribution of the patients with 2, 8-dihydroxyadenine urolithiasis and adenine phosphoribosyltransferase deficiency in Japan., J. Urol. in pressGoogle Scholar
  8. 8.
    S. Fujimori, I. Akaoka, K. Sakamoto, H. Yamanaka, K. Nishioka, and N. Kamatani, Common characteristics of mutant adenine phosphoribosyltransferases from four separate Japanese families with 2, 8-dihydroxyadenine urolithiasis associated with partial enzyme deficiencies., Hum. Genet. 71: 171 (1985).PubMedCrossRefGoogle Scholar
  9. 9.
    N. Kamatani, F. Takeuchi, Y. Nishida, H. Yamanaka, K. Nishioka, and K. Tatara, Fujimori, S., Kaneko. K. Akaoka. I. and. Tofuku. Y. Severe, impairment, in. adenine. metabolism, with. a. partial, deficiency, of. adenine. phosphoribosyltransferase. Metabolism 34: 164 (1985).PubMedCrossRefGoogle Scholar
  10. 10.
    S. Fujimori, I. Akaoka, F. Takeuchi, H. Kanayama, K. Tatara, K. Nishioka, and N. Kamatani, Altered kinetic properties of a mutant adenine phosphoribosyltransferase., Metabolism 35: 187 (1986).PubMedCrossRefGoogle Scholar
  11. 11.
    Y. Hidaka, S. A. Tarle, S. Fujimori, N. Kamatani, N. Kelley, and T. D. Pallella, Human adenine phosphoribosyltransferase (APRT) deficiency: Demonstration of a single mutant allele common to the Japanese., J. Clin. Invest. 81: 945 (1988).PubMedCrossRefGoogle Scholar
  12. 12.
    Y. Nishida, S. Hirano, and A. Miyamoto, adenine phosphoribosyltransferase in 2, 8-dihydroxyadenine urolithiasis., Arch. Intern. Med. 146: 2068 (1986).PubMedCrossRefGoogle Scholar
  13. 13.
    S. Abe, K. Hayasaka, K. Narisawa, K. Tada, G. Okada, H. Koyama, S. Kurosu, M. Kudoh, and K. Matsushita, Partial and complete adenine phosphoribosyltransferase deficiency associated with 2, 8-dihydroxyadenine urolithiasis: kinetic and immunochemical properties of APRT., Enzyme 37: 182 (1987).PubMedGoogle Scholar
  14. 14.
    T. Nobori, N. Kamatani, K. Mikanagi, Y. Nishida, and K. Nishioka, Establishment and characterization of B cell lines from individuals with various types of adenine phosphoribosyltransferase deficiencies., Biochem. Biophys. Res. Commun. 137: 998 (1986).PubMedCrossRefGoogle Scholar
  15. 15.
    N. Kamatani, S. Kuroshima, C. Terai, K. Kawai, K. Mikanagi, and K. Nishioka, Selection of human cells having two different types of mutations in individual cells (genetic/artificial mutants): Application to the diagnosis of the heterozygous state for a type of adenine phosphoribosyltransferase deficiency., Hum. Genet. 76: 148 (1987).PubMedCrossRefGoogle Scholar
  16. 16.
    M. K. Dush, J. M. Sikela, S. A. Khan, J. A. Tischfield, and P. J. Stambrook, Nucleotide sequence and organization of the mouse adenine phosphribosyltransferase gene: presence of a coding region common to animal and bacterial phosphoribosyltransferases that has a variable intron/exon arrangement., Proc. Natl. Acad. Sci. USA 82: 2731 (1985).PubMedCrossRefGoogle Scholar
  17. 17.
    B. Hove-Jensen, K. W. Harlow, C. J. King and R. L. Switzer, Phosphoribosylpyrophosphate synthetase of Escherichia coli. properties of the purified enzyme and primary structure of the prs gene. J. Biol. Chem. 261: 6765 (1986).PubMedGoogle Scholar
  18. 18.
    H. V. Hershey, and M. W. Taylor, Nucleotide sequence and deduced amino acid sequence of Escherichia coli adenine phosphoribosyltransferase and comparison with other analogous enzymes., Gene 43: 287 (1986).PubMedCrossRefGoogle Scholar
  19. 19.
    M. Taira, S. Ishijima, K. Kita, K. Yamada, T. Iizasa, and M. Tatibana, Nucleotide and deduced amino acid sequences of two distinct cDNAs for rat phosphoribosylpyrophosphate synthetase., J. Biol. Chem. 262: 14867 (1987).PubMedGoogle Scholar
  20. 20.
    P. J. Stambrook, M. K. Dush, J. J. Trill, and J. A. Tischfield, Cloning of a functional human adenine phosphoribosyltransferase (APRT) gene: Identification of a restirction fragment length polymorphism and preliminary analysis of DNAs from APRT-deficient families and cell mutants., Somat. Cell. Mol. Genet. 10: 359 (1984).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Naoyuki Kamatani
    • 1
  • Shoko Kuroshima
    • 1
  • Chihiro Terai
    • 1
  • Masayuki Hakoda
    • 1
  • Kusuki Nishioka
    • 1
  • Kiyonobu Mikanagi
    • 1
  1. 1.Institute of RheumatologyTokyo Women’s Medical CollegeTokyoJapan

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