X-Linked Recessive (Duchenne) Muscular Dystrophy (DMD) and Purine Metabolism: Effects of Oral Allopurinol and Adenylate

  • W. H. S. Thomson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 165)


DMD in males is the most common and disastrous form of the disease, with relentless rapid muscle loss leading to wheelchair life in childhood, progressive physical distortion and early death. It is transmitted as an X-linked recessive gene by healthy females, though one third of all cases and carriers are new mutants1. In the DMD male patient, the dystrophic X-chromosome performs alone in the multi-nucleated muscle fibre, with rapid wasting towards a fatal issue; but the female DMD carrier is unaffected, with rarely more than an attenuated manifestation like diagnostic serum creatine kinase (CK) elevations2, due to protection after Lyonisation by even a moderate proportion of muscle nuclei run by the normal paternal X-chromosome3,4. similar protection for DMD male muscle should be possible by restoring the essential substances so easily provided by normal but not by dystrophic nuclei. Evidence suggests that these substances are adenine nucleotides, acting through energy-carrying ATP (adenosine 5′-triphosphate) essential to every aspect of cell function.


Muscular Dystrophy Muscle Protein Synthesis Duchenne Muscular Dystrophy Nuclear Magnetic Resonance27 Disastrous Form 
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  1. 1.
    N. Yasuda and K. Kondo. No sex differences in mutation rates of Duchenne muscular dystrophy. 3 Pied Genet 17: 106 (1980).Google Scholar
  2. 2.
    I. Smith and W.H.S. Thomson. Carrier detection in X-linked recessive (Ouchenne) muscular dystrophy: pyruvate kinase isoenzymes and creatine Phosphokinase in serum and blood cells. Clin Chim Acta 78: 439 (1977).PubMedCrossRefGoogle Scholar
  3. 3.
    W.H.S. Thomson. J.C. Sweetin and T.E. Hilditch. Studies on the carrier state in X-linked recessive (Ouchenne) muscular dystrophy. Clin Chim Acta 63: 383 (1975).PubMedCrossRefGoogle Scholar
  4. 4.
    M.R. Gomez, A.G. Engel. G. Dewald and H.A. Peterson. Failure of inactivation of Duchenne dystrophy X-chromosome in one of female identical twins. Neurology 27: 537 (1977).PubMedCrossRefGoogle Scholar
  5. 5.
    P.J. Vignos, Jr. and J.L. Warner. Glycogen, creatine and high energy phosphate in human muscle disease. 3 Lab Clin Pled 62: 579 (1963).Google Scholar
  6. 6.
    L. Stengel-Rutkowski and W. Bartheimai. Über den Muskel-Energie-Stoffwechsel bei Kindern mit progressiver Muskeldystrophie Typ Duchenne. Klin Wschr 51: 957 (1973).PubMedCrossRefGoogle Scholar
  7. 7.
    W.H.S. Thomson and I. Smith. X-linked recessive (Duchenne) muscular dystrophy (DMD) and purine metabolism: effects of oral allopurinol and adenylate. Metabolism 27: 151 (1978).PubMedCrossRefGoogle Scholar
  8. 8.
    W.H.S. Thomson, J.C. Sweetin and I.J.D. Hamilton. ATP and muscle enzyme efflux after physical exertion. Clin Chim Acta 59: 241 (1975).PubMedCrossRefGoogle Scholar
  9. 9.
    J.D. Williams, B.M. Ansell, L. Reiffel, C.A. Stone and R.M. Kark. Electrolyte levels in normal and dystrophic muscle determined by neutron activation. Lancet ii:464 (1957).CrossRefGoogle Scholar
  10. 10.
    E. Spitzer, R. Grosse, V. Kuprijanov and A. Preobrazhensky. Demonstration of a digitalis-sensitive sarcolemmal Ca2+ pump functionally coupled with a membrane associated creatine Phosphokinase. Acta biol med germ 40: 1111 (1981).PubMedGoogle Scholar
  11. 11.
    C.J. Duncan. Role of intracellular calcium in promoting muscle damage: a strategy for controlling the dystrophic condition. Experientia 34: 1531 (1978).PubMedCrossRefGoogle Scholar
  12. 12.
    J.C. Sweetin and W.H.S. Thomson. Enzyme efflux and clearance. Clin Chim Acta 48: 403 (1973).PubMedCrossRefGoogle Scholar
  13. 13.
    J.H. Wilkinson and J.M. Robinson. Effect of ATP on release of intracellular enzymes from damaged cells. Nature 249: 662 (1974).PubMedCrossRefGoogle Scholar
  14. 14.
    W.H.S. Thomson. Serum enzyme studies in inherited disease of skeletal muscle. Clin Chim Acta 35: 183 (1971).PubMedCrossRefGoogle Scholar
  15. 15.
    M.J. Rennie, R.H.T. Edwards, D.D. Millward, S.L. Wolman, D. Halliday and D.E. Matthews. Effects of Duchenne muscular dystrophy on muscle protein synthesis. Nature 296: 165 (1982).PubMedCrossRefGoogle Scholar
  16. 16.
    C.A. Bonsett. Pseudohypertrophic muscular dystrophy: distribution of degenerative features as revealed by an anatomical study. Neurology 13: 728 (1963).PubMedCrossRefGoogle Scholar
  17. 17.
    N.S. Dhalla, M. Fedelesova and I. Toffler. Biochemical alterations in the skeletal muscle of vitamin E deficient rats. Canad 3 Biochem 49: 1202 (1971).CrossRefGoogle Scholar
  18. 18.
    M.A. Becker, R.C.K. Yen, P. Itkin, S.J. Goss, J.E. Seegmiller and B. Bakay. Regional localization of the gene for human phosphoribosylpyrophosphate synthetase on the X-chromosome. Science 203: 1016 (1979).PubMedCrossRefGoogle Scholar
  19. 19.
    N.L. Edwards. D. Recker, D. Airozo and I.H. Fox. Enhanced purine salvage during allopurinol therapy: an important pharmacologic property in humans. J Lab Clin Pied 98: 673 (1981).Google Scholar
  20. 20.
    J.L. Lilienthal. K.L. Zierler, B.P. Folk, R. Buka and M.J. Riley. A reference base and system for analysis of muscle constituents. J Biol Chem 182: 501 (1950).Google Scholar
  21. 21.
    H.U. Bergmeyer (ed.). “Methods of enzymatic analysis”, Academic, New York (1963). pp. 543, 573, 610.Google Scholar
  22. 22.
    R.H.T. Edwards. D.A. Jones, C. Maunder and G.J. Batra. Needle biopsy for muscle chemistry. Lancet i:736 (1975).CrossRefGoogle Scholar
  23. 23.
    F.J. Samaha. B. Davis and B. Nagy. Ouchenne muscular dystrophy: adenosine triphosphate and creatine phosphate content in muscle. Neurology 31: 916 (1981).PubMedCrossRefGoogle Scholar
  24. 24.
    W.H.S. Thomson and I. Smith. Allopurinol in Duchenne’s muscular dystrophy. New Eng J Med 299: 101 (1978).PubMedGoogle Scholar
  25. 25.
    Review article: Intestinal absorption of adenosine triphosphate. Nutrition Reviews 36: 309 (1978).Google Scholar
  26. 26.
    T.E. Stacey. Postnatal product replacement. In “Advances in the treatment of inborn errors of metabolism” p. 21. M.d’A. Crawfurd. D.A. Gibbs and R.W.E. Watts (eds.), Wiley, New York (1982).Google Scholar
  27. 27.
    R.J. Newman, P.D. Bore, L. Chan, D.G. Gadian, P. Styles, D. Taylor and G.K. Radda. Nuclear magnetic resonance studies of forearm muscle in Duchenne dystrophy. Brit Med J 284: 1072 (1982).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • W. H. S. Thomson
    • 1
  1. 1.Research LaboratoryKnightswood HospitalGlasgowUK

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