Skip to main content
SpringerLink
Log in
Book cover

Molecular Genetics, Biochemistry and Clinical Aspects of Inherited Disorders of Purine and Pyrimidine Metabolism pp 104–111Cite as

The Genetic and Metabolic Basis of ADA Deficiency

  • Conference paper

  • 111 Accesses

Abstract

It is nearly 20 years since the first report of adenosine deaminase (ADA) deficiency occurring with severe combined immunodeficiency disease (SCID) [1]. At the time, research on purine metabolism in human disease was focused on questions related to gout. Investigation of the Lesch-Nyhan syndrome and phosphoribosylpyrophosphate (PPRP) synthetase overactivity fit this paradigm well, providing insight into mechanisms responsible for causing purine overproduction and hyperuricemia. The discovery of an association between ADA deficiency and SCID was entirely unexpected and identified an apparently important, but enigmatic, role of purine nucleoside metabolism in the development and function of the immune system. It also highlighted a lack of understanding of the biochemical control of the immune system at a time when the existence and functions of distinct lymphocyte subsets were only beginning to be appreciated. Giblett’s report [1] and her subsequent discovery of purinenucleoside phosphorylase (PNP) deficiency with selective T cell dysfunction offered a novel and challenging direction for future research.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Giblett ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ (1972) Adenosine deaminase deficiency in two patients with severely impaired cellular immunity. Lancet 11: 1067–1069

    Article  Google Scholar 

  2. Kredich NM, Hershfield MS (1989) Immunodeficiency disease caused by adenosine deaminase deficieny and purine nucleoside Phosphorylase deficieny. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. McGraw- Hill, New York, pp 1045–1075

    Google Scholar 

  3. Daddona PE, Shewach DS, Kelley WN, Argos P, Markham AF, Orkin SH (1984) Human adenosine deaminase cDNA and complete primary amino acid sequence. J Biol Chem 259: 12101–12106

    PubMed  CAS  Google Scholar 

  4. Orkin SH, Dadonna PE, Shewach DS, Markham AF, Bruns GA, Goff SC, Kelley W (1983) Molecular cloning of human adenosine deaminase gene sequences. J Biol Chem 258: 12753–12756

    PubMed  CAS  Google Scholar 

  5. Valerio D, Duyvesteyn MGC, Meera Kahn P, van Kessel AG, de Waard A, van der Eb A (1983) Isolation of cDNA clones for human adenosine deaminase. Gene 25: 231–240

    CAS  Google Scholar 

  6. Wiginton DA, Adrian GS, Friedman D, Suttle DP, Hutton JJ (1983) Cloning of cDNA sequences of human adenosine deaminase. Proc Natl Acad Sci USA 80: 7481–7485

    Article  PubMed  CAS  Google Scholar 

  7. Wiginton DA, Adrian GS, Hutton J J (1984) Sequence of human adenosine deaminase cDNA including the coding region and a small intron. Nucl Acid Res 12: 2439–2446

    Article  CAS  Google Scholar 

  8. Williams SR, Goddard JM, Martin DWJ (1984) Human purine nucleoside Phosphorylase cDNA sequence and genomic clone characterization. Nucl Acids Res 12: 5779–5787

    Article  PubMed  CAS  Google Scholar 

  9. Goddard JM, Caput D, Williams SR, Martin DWJ (1983) Cloning of human purine nucleoside phosphorylase cDNA sequences by complementation in Escherichia coli. Proc Natl Acad Sei USA 80: 4281–4285

    Article  CAS  Google Scholar 

  10. Wiginton DA, Kaplan DJ, States JC; Akeson AL, Perme CM, Bilyk IJ, Vaughn AJ, Lattier DL, Hutton J J (1986) Complete sequence and structure of the gene for human adenosine deaminase. Biochem 25: 8234–8244

    Article  CAS  Google Scholar 

  11. Ealick SE, Rule SA, Carter DC, Greenhough TJ, Babu YS, Cook WJ, Habash J, Helliwell JR, Stoeckler JD, Parks REJ, Chen S-F, Bugg CE (1990)Three dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 Ä resolution. J Biol Chem 265: 1812–1820

    Google Scholar 

  12. Wilson DK, Rudolph FB, Quiocho FA (1991) Atomic structure of adenosine deaminase complexed with a transition-state analog: understanding catalysis and immunodeficiency mutations. Science 252: 1278–1284

    Article  PubMed  CAS  Google Scholar 

  13. Jahnwar SC, Berkvens TM, Breukel C, van Ormondt H, van der Eb AJ, Kahn PM (1989) Localization of human adenosine deaminase (ADA) gene sequences to the ql2-ql3.11 region of chromosome 20 by in situ hybridization. Cytogenet Cell Genet 50: 168–171

    Article  Google Scholar 

  14. Chang ZY, Nygaard P, Chinault AC, Kellems RE (1991) Deduced amino acid sequence of Escherichia coli adenosine deaminase reveals evolutionarily conserved amino acid residues: implications for catalytic function. Biochem 30: 2273–2280

    Article  CAS  Google Scholar 

  15. Markert ML, Hutton JJ, Wiginton DA, States JC, Kaufman RE (1988) Adenosine deaminase ( ADA) deficiency due to deletion of the ADA gene promoter and first exon by homologous recombination between two Alu elements. J Clin Invest 81: 1323–1327

    Google Scholar 

  16. Berkvens TM, van Ormondt H, Gerritsen EJ, Meera Khan P, van der Eb A J (1990) Identical 3250-bp deletion between two Alul repeats in the ADA genes of unrelated ADA-SCID patients. Structural and functional analysis of the murine adenosine deaminase gene. Genomics 7: 476–485

    Google Scholar 

  17. Akeson AL, Wiginton DA, Dusing MR, States JC, Hutton JJ (1988) Mutant human adenosine deaminase alleles and their expression by transfection into fibroblasts. J Biol Chem 263: 16291–16296

    PubMed  CAS  Google Scholar 

  18. Akeson AL, Wiginton DA, States JC, Perme CM, Dusing MR, Hutton JJ (1987) Mutations in the human adenosine deaminase gene that affect protein structure and RNA splicing. Proc Natl Acad Sci USA 84: 5947–5951

    Article  PubMed  CAS  Google Scholar 

  19. Bonthron DT, Markham AF, Ginsberg D, Orkin SH (1985) Identification of a point mutation in the adenosine deaminase gene responsible for immunodeficieny. J Clin Invest 76: 894–897

    Article  PubMed  CAS  Google Scholar 

  20. Hirschhorn R, Chakravarti V, Puck J, Douglas SD (1991) Homozygosity for a newly identified missense mutation in a patient with very severe combined immunodeficiency due to adenosine deaminase deficiency ( ADA-SCID ). Am J Hum Genet 49: 878–885

    Google Scholar 

  21. Markert ML, Norby SC, Ward FE (1989) A high proportion of AD A point mutations associated with a specific alanine-to-valine substitution. Am J Hum Genet 45: 345–361

    Google Scholar 

  22. Valerio D, Dekker BMM, Duyvesteyn MGC, van der Voorn L, Berkvens TM, van Ormondt H, van der Eb AJ (1986) One adenosine deaminase allele in a patient with severe combined immunodeficiency contains a point mutation abolishing enzyme activity. Embo J 5: 113–119

    PubMed  CAS  Google Scholar 

  23. Hirschhorn R, Tzall S, Ellenbogen A, Orkin SH (1989) Identification of a point mutation resulting in a heat-labile adenosine deaminase ( ADA) in two unrelated children with partial ADA deficiency. J Clin Invest 83: 497–501

    Google Scholar 

  24. Hirschhorn R, Tzall S, Ellenbogen A (1990) Hot spot mutations in adenosine deaminase deficiency. Proc Natl Acad Sci USA 87: 6171–6175

    Article  PubMed  CAS  Google Scholar 

  25. Arredondo-Vega FX, Kurtzberg J, Chaffee S, Santisteban I, Reisner E, Povey MS, Hershfield MS (1990) Paradoxical expression of adenosine deaminase in T cells cultured from a patient with adenosine deaminase deficiency and combined immunodeficiency. J Clin Invest 86: 444–452

    Article  PubMed  CAS  Google Scholar 

  26. Polmar SH, Stern RC, Schwartz AL, Wetzler EM, Chase PA, Hirschhorn R (1976) Enzyme replacement therapy for adenosine deaminase deficiency and severe combined immunodeficiency. N Engl J Med 295: 1337–1343

    Article  PubMed  CAS  Google Scholar 

  27. Polmar SH (1980) Metabolic aspects of immunodeficiency disease. Semin Hematol 17: 30–43

    PubMed  CAS  Google Scholar 

  28. Hirschhorn R (1990) Adenosine deaminase deficiency. In: Rosen FS, Seligmann M (eds) Immunodeficiency reviews. Harwood Academic, New York, pp 175–198

    Google Scholar 

  29. Fischer A, Landais P, Friedrich W, Morgan G, Gerritsen B, Fasth A, Porta F, Griscelli C, Goldman SF, Levinsky R, Vossen J (1990) European experience of bone marrow transplantation for severe combined immunodeficiency. Lancet 336: 850–854

    Article  PubMed  CAS  Google Scholar 

  30. O’Reilly RJ, Keever CA, Small TN, Brochstein J (1989) The use of HLA-non-identicalT-cell-depleted marrow for transplant for correction of severe combined immunodeficiency disease. Immunodeficiency Rev 1: 2732013–309

    Google Scholar 

  31. Hershfield MS (1991) Enzyme replacement therapy for inherited metabolic diseases. In: FriedmannT(ed)Therapy for genetic disease. Oxford University Press, Oxford, pp 76–94

    Google Scholar 

  32. Abuchowski A, McCoy JR; Palczuk NC, van Es T, Davis FF (1977) Effect of attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catal- ase. J Biol Chem 252: 3582–2586

    PubMed  CAS  Google Scholar 

  33. Abuchowski A, van Es T, Palczuk NC, Davis FF (1977) Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. J Biol Chem 252: 3578–3581

    PubMed  CAS  Google Scholar 

  34. Davis S, Abuchowski A, Park YK, Davis FF (1981) Alteration of the circulating life and antigenic properties of bovine adenosine deaminase in mice by attachment of polyethylene glycol. Clin Exp Immunol 46: 649–652

    PubMed  CAS  Google Scholar 

  35. Hershfield MS, Buckley RH, Greenberg ML, Melton AL, Schiff R, Hatem C, Kurtzberg J, Markert ML, Kobayashi RH, Kobayashi AL, Abuchowski A (1987) Treatment of adenosine deaminase deficiency with polyethylene glycol-modified adenosine deaminase. N Engl J Med 316: 589–596

    Article  PubMed  CAS  Google Scholar 

  36. Bory C, Boulieu R, Souillet G, Chantin C, Rolland MO, Mathieu M, Hershfield MS (1990) Comparison of red cell transfusion and polyethylene glycol-modified adenosine deaminase therapy in an adenosine deaminase-deficient child. Ped Res 28: 127–130

    CAS  Google Scholar 

  37. Levy Y, Hershfield MS, Fernandez-Mejia C, Polmar SH, Scudiery D, Berger M, Sorensen RU (1988) Adenosine deaminase deficiency with late onset of recurrent infections: response to treatment with polyethylene glycol-modified adenosine deaminase ( PEG-ADA ). J Pediatr 113: 312–317

    Google Scholar 

  38. Hershfield MS, Chaffee S (1991) PEG-enzyme replacement therapy for adenosine deficiency. In: Desnick RJ (ed) Treatment of genetic disease. Churchill Livingstone, New York, pp 169–182

    Google Scholar 

Download references

Authors
  1. M. S. Hershfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. X. Arredondo-vega
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. Santisteban
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. Chaffee
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Medizinische Poliklinik, Universität München, Pettenkoferstr. 8 a, 80336, München, Germany

    Ursula Gresser

Rights and permissions

Reprints and permissions

Copyright information

© 1993 Springer Verlag, Berlin Heidelberg

About this paper

Cite this paper

Hershfield, M.S., Arredondo-vega, F.X., Santisteban, I., Chaffee, S. (1993). The Genetic and Metabolic Basis of ADA Deficiency. In: Gresser, U. (eds) Molecular Genetics, Biochemistry and Clinical Aspects of Inherited Disorders of Purine and Pyrimidine Metabolism. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84962-6_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-84962-6_15

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-84964-0

  • Online ISBN: 978-3-642-84962-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation