Human Myoadenylate Deaminase Deficiency

  • William N. Fishbein
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 165)


This entity was first described, in 5 patients, in 1978, as the consequence of the introduction of an effective histoenzymatic stain1 for adenylate deaminase in frozen muscle biopsies. That report2 established the following: (1) The deficiency state was quite common, occurring in 1–2% of muscle biopsies, and accompanied by relatively mild, though persistent, symptoms of exertional myalgia. (2) Application of a sensitive solution assay3 verified that all 5 cases had less than 5% of the specific activity of adenylate deaminase in normal muscle biopsies, thus validating the histoenzymatic stain as a diagnostic tool. (3) There was no evidence of an enzyme inhibitor, by crossmixing studies of normal and deficient homogenates. (4) Affected patients had normal levels of adenylate deaminase in their red cells, indicating separate genetic control of the two isozymes. (5) Affected patients had normal skeletal muscle architecture and normal levels of other enzymes, indicating that the enzyme deficiency was specific, and was clearly not the cause of muscular dystrophy, as had often been suggested. (6) A simple provocative procedure, the lactateammonia-exercise-ratio (LAER test) demonstrated the physiological deficit in affected patients, and could be used for clinical diagnosis. (7) Skeletal muscle adenylate deaminase could be separated and identified, in its native state, by proper application of PAGE and the catalytic stain.


Muscular Dystrophy Muscle Biopsy Deficiency State Malignant Hyperthermia Purine Nucleotide Cycle 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Fishbein,.W.N., J.L. Griffin, and V.W. Armbrustmacher, 1980. Stain for skeletal muscle adenylate deaminase: an effective tetrazolium stain for frozen biopsy specimens. Arch. Path. Lab. Med. 104: 462–466.PubMedGoogle Scholar
  2. 2.
    Fishbein, W.N., V.W. Armbrustmacher, and J.L. Griffin. 1978. Myoadenylate deaminase deficiency: A new disease of muscle. Science. 299: 545–548.CrossRefGoogle Scholar
  3. 3.
    Fishbein, W.N. 1979. Indicator enzyme assays. I. Adenylate deaminase: principles and application to human muscle biopsies and blood cells. Biochem. Med. 22: 307–322.PubMedCrossRefGoogle Scholar
  4. 4.
    Ashby, B., C. Frieden, and R. Bischoff. 1979. Immunofluorescent and histochemical localization of AMP deaminase in skeletal muscle. J. Cell Biol. 81: 361–373.PubMedCrossRefGoogle Scholar
  5. 5.
    Meyer, R.A., J. Gilloteaux, and R.L. Terjung. 1980. Histo-chemical demonstration of differences in AMP deaminase activity in rat skeletal muscle fibers. Experientia. 36: 676–677.PubMedCrossRefGoogle Scholar
  6. 6.
    Keleman, J., D.R. Rice, W.G. Bradley, T.L. Munsat, S. DiNauro, and E.L. Hogan, 1982. Familial myoadenylate deaminase deficiency and exertional myalgias. Neurology. 32: In press.Google Scholar
  7. 7.
    DiMauro, S., A.F. Miranda, A.P. Hays, W.A. Franck, G.S. Hoffman, R.S. Schoenfeldt, and N. Singh. 1980. Myoadenylate deaminase deficiency. Muscle biopsy and muscle culture in a patient with gout. J. Neurol. Sci. 47: 191–202.Google Scholar
  8. 8.
    Sabina, R.L., J. L. Swain, B. M. Patten, T. Ashizawa, W.E. O’Brien, and E.W. Holmes. 1980. Disruption of the purine nucleotide cycle. A potential explanation for muscle dysfunction in myoadenylate deaminase deficiency. J. Clin. Invest. 66: 1419–1423.PubMedCrossRefGoogle Scholar
  9. 9.
    Mercelis, R., J.J. Martin, I. Dehaene, Th. deBarsy, and G. Van den Berghe. 1981. Myoadenylate deaminase deficiency in a patient with facial and limb girdle myopathy. J. Neurol. 225: 157–166.PubMedCrossRefGoogle Scholar
  10. 10.
    Hayes, D.J., B.A. Summers, and J.A. Morgan-Hughes. 1982. Myoadenylate deaminase deficiency or not? Observations on two brothers with exercise-induced muscle pain. J. Neurol. Sci. 53: 125–136.PubMedCrossRefGoogle Scholar
  11. 11.
    Shumate, J. B., K.K. Kaiser, J.E. Carroll, and M. H. Brooke. 1980. Adenylate deaminase deficiency in a hypotonic infant. J. Pediatr. 96: 885–887.PubMedCrossRefGoogle Scholar
  12. 12.
    Shumate, J.B., R. Katnik, M. Ruiz, K. Kaiser, C. Frieden, M. H. Brooke, and J.E. Carroll. 1979. Myoadenylate deaminase deficiency. Muscle and Nerve. 2: 213–216.PubMedCrossRefGoogle Scholar
  13. 13.
    Kar, N.C., and C.M. Pearson. 1981. Muscle adenylate deaminase deficiency. Report of six new cases. Arch. Neurol. 38: 279–281.Google Scholar
  14. 14.
    Scholte, H.R., H.F.M. Busch, and I.E.M. Luyt-Houwen. 1981. Familial AMP deaminase deficiency with skeletal muscle type I atrophy and fatal cardiomyopathy. J. Inher. Metab. Dis. 4: 169–170.CrossRefGoogle Scholar
  15. 15.
    Fishbein, W.N., J.L. Griffin, K. Nagarajan, J.W. Winkert, and V.W. Armbrustmacher. 1979. Immunologic uniqueness of muscle adenylate deaminase and genetic transmission of the deficiency state. Clin. Res. 27: 274A.Google Scholar
  16. 16.
    Fishbein, W.N., J. I. Davis, K. Nagarajan, J.W. Winkert, and J.W. Foellmer. 1980. Immunologic distinction of human muscle adenylate deaminase from the isozyme(s) in human peripheral blood cells: implications for myoadenylate deaminase deficiency. Arch. Biochem. Biophys. 205: 360–364.PubMedCrossRefGoogle Scholar
  17. 17.
    Fishbein, W.N., and J.I. Davis. 1982. Immunologic and kinetic evaluation of myoadenylate deaminase deficiency. Fed. Proc. ( USA ). 41: 902.Google Scholar
  18. 18.
    Ogasawara, N., H. Goto, Y. Yamada, T. Watanabe, and T. Asano. 1982. AMP deaminase isozymes in human tissues. Biochim. Biophys. Acta. 714: 298–306.PubMedCrossRefGoogle Scholar
  19. 19.
    Fishbein, W.N., V. W. Armbrustmacher, and J.L. Griffin. 1981. Myoadenylate deaminase deficiency; verification on repeat biopsy, fresh or frozen, and origin of the residual enzyme. IRCS Med. Sci. 9: 103–104.Google Scholar
  20. 20.
    Davuluri, S.P., F.J.R. Hird, and I.J. Stanley. 1981. On the significance of adenylic acid aminohydrolase in skeletal muscle of vertebrates. Comp. Biochem. Physiol. 68B: 369–375.Google Scholar
  21. 21.
    Chapman, A.G., A.L. Miller, and D.E. Atkinson. 1976. Role of the adenylate deminase reaction in regulation of adenine nucleotide metabolism in Ehrlich ascites tumor cells. Cancer Res. 36: 1144–1150.PubMedGoogle Scholar
  22. 22.
    Koretz, J.F., and C. Frieden. 1980. Adenylate deaminase binding to synthetic thick filaments of myosin. Proc. Natl. Acad. Sci. ( USA ). 77: 7186–7188.PubMedCrossRefGoogle Scholar
  23. 23.
    Shiraki, H., S. Miyamoto, Y. Matsuda, E. Momose, and H. Nakagawa. 1981. Possible correlation between binding of muscle type AMP deaminase to myofibrils and ammoniagenesis in rat skeletal muscle on electrical stimulation. Biochem. Biophys. Res. Comm. 100: 1099–1103.PubMedCrossRefGoogle Scholar
  24. 24.
    Aragon, J.J., K. Tornheim, and J.M. Lowenstein. 1980. On a possible role of IMP in the regulation of phosphorylase activity in skeletal muscle. FEBS Lett. 117 Suppl: K56 - K64.Google Scholar
  25. 25.
    Liang, C.-M., Y.P. Liu, and B.A. Chabner. 1980. Modes of action of hypoxanthine, inosine and inosine 5’-monophosphate on cyclic nucleotide phosphodiesterase from bovine brain. Biochem. Pharmacol. 29: 277–282.PubMedCrossRefGoogle Scholar
  26. 26.
    Buchwald, M., B. Ullman, and D.W. Martin, Jr. 1981. Biochemical and genetic analysis of AMP deaminase deficiency in cultured mammalian cells. J. Biol. Chem. 256: 10346–10353.PubMedGoogle Scholar
  27. 27.
    Aragon, J.J., and J.M. Lowenstein. 1980. The purine nucleotide cycle. Comparison of the levels of citric acid intermediates with the operation of the purine nucleotide cycle in rat skeletal muscle during exercise and recovery from exercise. Eur. J. Biochem. 110: 371–377.PubMedCrossRefGoogle Scholar
  28. 28.
    Meyer, R.A., and R.L. Terjung. 1980. AMP deamination and IMP reamination in working skeletal muscle. Am. J. Physiol. 239: C32 - C38.PubMedGoogle Scholar
  29. 29.
    Holmes, E.W., et al. These Proceedings.Google Scholar
  30. 30.
    Brosh, S., P. Boer, E. Zoref-Shani, and 0. Sperling. 1982. De novo purine synthesis in skeletal muscle. Biochim. Biophys. Acta. 714: 181–183.PubMedCrossRefGoogle Scholar
  31. 31.
    Fishbein, W.N., V.W. Armbrustmacher, and J.L. Griffin. 1980. Skeletal muscle adenylate deaminase, adenylate kinase, and creatine kinase in myoadenylate deaminase deficiency and malignant hyperthermia. Clin. Res. 28: 288A.Google Scholar
  32. 32.
    Fishbein, W.N., J.I. Davis, K. Nagarajan, and M.J. Smith. 1981. Specific serum/plasma inhibitor of muscle adenylate deaminase. IRCS Med. Sci. 9: 178–179.Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • William N. Fishbein
    • 1
  1. 1.Biochemistry DivisionArmed Forces Institute of PathologyUSA

Personalised recommendations