Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1980 Jan;65(1):103–108. doi: 10.1172/JCI109639

Erythrocyte metabolism in purine nucleoside phosphorylase deficiency after enzyme replacement therapy by infusion of erythrocytes.

G E Staal, J W Stoop, B J Zegers, L H Siegenbeek van Heukelom, M J van der Vlist, S K Wadman, D W Martin
PMCID: PMC371344  PMID: 6765955

Abstract

Purine nucleoside phosphorylase deficiency is associated with a severely defective T-cell immunity. A patient with purine nucleoside phosphorylase deficiency was treated with transfusions of irradiated erythrocytes and plasma. This resulted in a remarkable correction of the metabolic disturbances in the patient. The urinary excretion of inosine, deoxyinosine, guanosine, and deoxyguanosine decreased, whereas uric acid excretion as well as serum uric acid concentration increased. It could be shown that the enzyme activity of the circulating erythrocytes correlated inversely with the urinary excretion of nucleosides and directly with the excretion of uric acid. As a consequence of the therapy, several glycolytic intermediates of the erythrocytes were increased, especially 2,3-diphosphoglycerate. The high 2,3-diphosphoglycerate level caused a shift to the right of the oxygen dissociation curve (P50 = 32.9 mm Hg). The immunological status of the patient showed definite improvement after the enzyme replacement therapy.

Full text

PDF
103

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beutler E. 2,3-diphosphoglycerate affects enzymes of glucose metabolism in red blood cells. Nat New Biol. 1971 Jul 7;232(27):20–21. doi: 10.1038/newbio232020a0. [DOI] [PubMed] [Google Scholar]
  2. Carapella-de Luca E., Aiuti F., Lucarelli P., Bruni L., Baroni C. D., Imperato C., Roos D., Astaldi A. A patient with nucleoside phosphorylase deficiency, selective t-cell deficiency, and autoimmune hemolytic anemia. J Pediatr. 1978 Dec;93(6):1000–1003. doi: 10.1016/s0022-3476(78)81237-2. [DOI] [PubMed] [Google Scholar]
  3. Cohen A., Doyle D., Martin D. W., Jr, Ammann A. J. Abnormal purine metabolism and purine overproduction in a patient deficient in purine nucleoside phosphorylase. N Engl J Med. 1976 Dec 23;295(26):1449–1454. doi: 10.1056/NEJM197612232952603. [DOI] [PubMed] [Google Scholar]
  4. Cohen A., Gudas L. J., Ammann A. J., Staal G. E., Martin D. W., Jr Deoxyguanosine triphosphate as a possible toxic metabolite in the immunodeficiency associated with purine nucleoside phosphorylase deficiency. J Clin Invest. 1978 May;61(5):1405–1409. doi: 10.1172/JCI109058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cohen A., Hirschhorn R., Horowitz S. D., Rubinstein A., Polmar S. H., Hong R., Martin D. W., Jr Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine deaminase deficiency. Proc Natl Acad Sci U S A. 1978 Jan;75(1):472–476. doi: 10.1073/pnas.75.1.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gelfand E. W., Dosch H. M., Biggar W. D., Fox I. H. Partial purine nucleoside phosphorylase deficiency. Studies of lymphocyte function. J Clin Invest. 1978 Apr;61(4):1071–1080. doi: 10.1172/JCI109006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Giblett E. R., Ammann A. J., Wara D. W., Sandman R., Diamond L. K. Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity. Lancet. 1975 May 3;1(7914):1010–1013. doi: 10.1016/s0140-6736(75)91950-9. [DOI] [PubMed] [Google Scholar]
  8. Minakami S., Suzuki C., Saito T., Yoshikawa H. Studies on erythrocyte glycolysis. I. Determination of the glycolytic intermediates in human erythrocytes. J Biochem. 1965 Dec;58(6):543–550. doi: 10.1093/oxfordjournals.jbchem.a128240. [DOI] [PubMed] [Google Scholar]
  9. Polmar S. H., Stern R. C., Schwartz A. L., Wetzler E. M., Chase P. A., Hirschhorn R. Enzyme replacement therapy for adenosine deaminase deficiency and severe combined immunodeficiency. N Engl J Med. 1976 Dec 9;295(24):1337–1343. doi: 10.1056/NEJM197612092952402. [DOI] [PubMed] [Google Scholar]
  10. Pritchard J. B., Chavez-Peon F., Berlin R. D. Purines: supply by liver to tissues. Am J Physiol. 1970 Nov;219(5):1263–1267. doi: 10.1152/ajplegacy.1970.219.5.1263. [DOI] [PubMed] [Google Scholar]
  11. Stoop J. W., Eijsvoogel V. P., Zegers B. J., Blok-Schut B., van Bekkum D. W., Ballieux R. E. Selective severe cellular immunodeficiency. Effect of thymus transplantation and transfer factor administration. Clin Immunol Immunopathol. 1976 Nov;6(3):289–298. doi: 10.1016/0090-1229(76)90081-7. [DOI] [PubMed] [Google Scholar]
  12. Stoop J. W., Zegers B. J., Hendrickx G. F., van Heukelom L. H., Staal G. E., de Bree P. K., Wadman S. K., Ballieux R. E. Purine nucleoside phosphorylase deficiency associated with selective cellular immunodeficiency. N Engl J Med. 1977 Mar 24;296(12):651–655. doi: 10.1056/NEJM197703242961203. [DOI] [PubMed] [Google Scholar]
  13. Ullman B., Gudas L. J., Clift S. M., Martin D. W., Jr Isolation and characterization of purine-nucleoside phosphorylase-deficient T-lymphoma cells and secondary mutants with altered ribonucleotide reductase: genetic model for immunodeficiency disease. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1074–1078. doi: 10.1073/pnas.76.3.1074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. van Heukelom L. H., Staal G. E., Stoop J. W., Zegers B. J. An abnormal form of purine nucleoside phosphorylase in a family with a child with severe defective T-cell-and normal B-cell immunity. Clin Chim Acta. 1976 Oct 1;72(1):117–124. doi: 10.1016/0009-8981(76)90042-5. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES