Advertisement

Purine Nucleoside Phosphorylase (PNP) Deficiency: A Therapeutic Challenge

  • A. R. Watson
  • H. A. Simmonds
  • D. R. Webster
  • L. Layward
  • D. I. K. Evans
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 165)

Abstract

Purine nucleoside phosphorylase (PNP:EC 2.4.2.1) deficiency appears to result in a predominantly T cell immune defect1. Lack of the PNP enzyme leads to the inability to degrade deoxynucleosides, particularly deoxyguanosine (dGR) resulting in the intracellular accumulation of deoxyguanosine triphosphate (dGTP) which is known to inhibit DNA synthesis in vitro2. Deoxycytidine kinase is considered responsible for the initial conversion of dGR to dGMP1. Hence deoxycytidine (dCR), the preferred substrate, should competitively inhibit dGTP accumulation as has been demonstrated in vitro1,2. However, oral dCR therapy for six months in a PNP deficient child produced no clinical or immunological improvement, probably due to degradation in the gut or rapid deamination3.

Keywords

High Pressure Liquid Chromatography Purine Nucleoside Phosphorylase Amniotic Epithelial Cell Inactivate Polio Vaccine Deoxy Inosine 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Enzyme defects and Immunodysfunction. Ciba Symposium 1968 (new series) Amsterdam. Excerpta Medica (1979).Google Scholar
  2. 2.
    D.A. Carson, J. Kaye, J.E. Seegmiller, Pathogenetic mechanisms in deficiencies of adenoside deaminase and purine nucleoside phosphorylase. In: Inborn errors of immunity and phagocytosis. Gutthler F., Seakins J.W.T., Harkness R.A., eds. Lancaster: MTP Press, 129 (1979).CrossRefGoogle Scholar
  3. 3.
    J.W. Stoop, B.J.M. Zegers, W. Kuis, C.J. Heijen, J.J. Roord, M. Duran, S.K.Wadman,G.E.J.Staal, Purine Nucleoside Phosphorylase Deficiency: Long Term Clinical, Immunological and Metabolic Follow-up. In: Primary Immunodeficiencies. Elsevier. Amsterdam 301, (1980).Google Scholar
  4. 4.
    A.R. Watson, D.I.K. Evans, H.B. Marsden, V. Miller, P.A. Rogers. Purine nucleoside phosphorylase deficiency associated with a fatal lymphoproliferative disorder. Arch.Dis.Child. 56: 7; 563 (1981).PubMedCrossRefGoogle Scholar
  5. 5.
    H.A. Simmonds, A.R. Watson, D.R. Webster, A. Sahota, D. Perrett. GTP depletion and other erythrocyte abnormalities in inherited PNP deficiency. Biochem. Pharmac. 31, 941 (1982).CrossRefGoogle Scholar
  6. 6.
    K.C. Rich, E. Mejians, I.H. Fox. Purine nucleoside phosphorylase deficiency: improved metabolic and immunological function with erythrocyte transfusion. N.Eng.J.Med. 303: 973 (1980).CrossRefGoogle Scholar
  7. 7.
    C.A. Akle, K.I. Welsh, M. Asdinolfi, S. Leibowitz, I. McColl. Immunogenicity of Human Amniotic Epithelial Cells after Transplantation into Volunteers. Lancet 11: 1003 (1981).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • A. R. Watson
    • 1
  • H. A. Simmonds
    • 1
  • D. R. Webster
    • 1
  • L. Layward
    • 1
  • D. I. K. Evans
    • 1
  1. 1.Departments of Child Health and Immunology and Purine LaboratoryRoyal Manchester Children’s Hospital and Guy’s Hospital Medical SchoolLondonUK

Personalised recommendations