Search tips
Search criteria 


Logo of jcinvestThe Journal of Clinical Investigation
J Clin Invest. 1977 September; 60(3): 741–746.
PMCID: PMC372419

Purine Nucleoside Phosphorylase Deficiency



Purine-nucleoside phosphorylase (NP) deficiency is associated with severely defective thymus-derived (T)-cell and normally functioning bone marrow-derived (B)-cell immunity. In this study, two unrelated families with a total of three NP deficient members were investigated.

High pressure liquid chromatography of the plasma of the three patients showed inosine levels greater than 66 μM. This nucleoside was absent from the plasma of their parents and control samples.

NP was purified from normal human erythrocytes by affinity chromatography and an antiserum prepared in rabbits was used to study the NP variants in the two families.

In family M the patient had no detectable erythrocyte NP activity and no detectable immunological-reacting material (irm) to the NP antibody. The parents, who are second cousins, had less than one-half of normal enzyme activity and approximately 14% irm attributable to a variant protein. Their electrophoretic patterns revealed a series of isozymes with slower than normal migration.

In family B the patients had 0.5% residual enzyme activity and about one-half normal irm. Their electrophoretic pattern showed faintly staining bands which migrated faster than normal NP. The mother of the patients had one-half normal enzyme activity, 11% irm attributable to her variant protein, and a normal electrophoretic pattern. The father had less than one-half normal enzyme activity, equal amounts of normal and variant irm, and an electrophoretic pattern that showed increased activity of the more rapidly migrating isozyme bands.

The combined use of immunological and electrophoretic techniques has shown the presence of three separate mutations; one in family M and two in family B associated with severely defective T-cell function.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (995K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Kim BK, Cha S, Parks RE., Jr Purine nucleoside phosphorylase from human erythroyctes. II. Kinetic analysis and substrate-binding studies. J Biol Chem. 1968 Apr 25;243(8):1771–1776. [PubMed]
  • George DL, Francke U. Gene dose effect: regional mapping of human nuceloside phosphorylase on chromosome 14. Science. 1976 Nov 19;194(4267):851–852. [PubMed]
  • Agarwal RP, Parks RE., Jr Purine nucleoside phosphorylase from human erythrocytes. IV. Crystallization and some properties. J Biol Chem. 1969 Feb 25;244(4):644–647. [PubMed]
  • Edwards YH, Edwards PA, Hopkinson DA. A trimeric structure for mammalian purine nucleoside phosphorylase. FEBS Lett. 1973 Jun 1;32(2):235–237. [PubMed]
  • Edwards YH, Hopkinson DA, Harris H. Inherited variants of human nucleoside phosphorylase. Ann Hum Genet. 1971 May;34(4):395–408. [PubMed]
  • Giblett ER, Ammann AJ, Wara DW, Sandman R, Diamond LK. 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. [PubMed]
  • van Heukelom LH, Staal GE, Stoop JW, Zegers BJ. 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. [PubMed]
  • Cohen A, Doyle D, Martin DW, Jr, Ammann AJ. 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. [PubMed]
  • Scott CR, Chen SH, Giblett ER. Detection of the carrier state in combined immunodeficiency disease associated with adenosine deaminase deficiency. J Clin Invest. 1974 Apr;53(4):1194–1196. [PMC free article] [PubMed]
  • Krenitsky TA, Elion GB, Henderson AM, Hitchings GH. Inhibition of human purine nucleoside phosphorylase. Studies with intact erythrocytes and the purified enzyme. J Biol Chem. 1968 Jun 10;243(11):2876–2881. [PubMed]
  • Osborne WR, Spencer N. Partial purification and properties of the common inherited forms of adenosine deaminase from human erythrocytes. Biochem J. 1973 May;133(1):117–123. [PubMed]
  • Harboe N, Ingild A. Immunization, isolation of immunoglobulins, estimation of antibody titre. Scand J Immunol Suppl. 1973;1:161–164. [PubMed]
  • Weeke B. Rocket immunoelectrophoresis. Scand J Immunol Suppl. 1973;1:37–46. [PubMed]
  • Weeke B. A manual of quantitative immunoelectrophoresis. Methods and applications. 1. General remarks on principles, equipment, reagents and procedures. Scand J Immunol Suppl. 1973;1:15–35. [PubMed]
  • Stoop JW, Zegers BJ, Hendrickx GF, van Heukelom LH, Staal GE, de Bree PK, Wadman SK, Ballieux RE. Purine nucleoside phosphorylase deficiency associated with selective cellular immunodeficiency. N Engl J Med. 1977 Mar 24;296(12):651–655. [PubMed]
  • Turner BM, Fisher RA, Harris H. An association between the kinetic and electrophoretic properties of human purine-nucleoside-phosphorylase isozymes. Eur J Biochem. 1971 Dec;24(2):288–295. [PubMed]
  • Funakoshi S, Deutsch HF. Human carbonic anhydrases. II. Some physicochemical properties of native isozymes and of similar isozymes generated in vitro. J Biol Chem. 1969 Jul 10;244(13):3438–3446. [PubMed]
  • Ullman B, Cohen A, Martin DW. Characterization of a cell culture model for the study of adenosine deaminase- and purine nucleoside phosphorylase-deficient immunologic disease. Cell. 1976 Oct;9(2):205–211. [PubMed]
  • Giblett ER. Immune cell function and recycling of purines. N Engl J Med. 1976 Dec 9;295(24):1375–1376. [PubMed]

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