A Case with Purine Nucleoside Phosphorylase Deficiency Suffering from Late-Onset Systemic Lupus Erythematosus and Lymphoma



Purine nucleoside phosphorylase (PNP) deficiency accounts for about 4% of severe combined immunodeficiency diseases. PNP deficiency is a variable disease with recurrent infections and neurodevelopmental delay. Autoimmunity and malignancy can still occur in one-third of patients.


Case report.

Case Presentation

An 8-year-old Saudi female who was apparently healthy presented at the age of 7 years with confirmed systemic lupus erythematosus (SLE) and lupus nephritis that were poorly controlled with conventional therapy. She also had frequent sinopulmonary and varicella infections. Preliminary immunological workup showed severe lymphopenia and depressed lymphocyte proliferation assay. The uric acid was within normal levels at 179 μmol/L (normal range, 150 to 350 μmol/L) 6 weeks after blood transfusion. Genetic study revealed a homozygous missense mutation c.265G>A in the PNP gene, resulting in a substitution of glutamic acid to lysine at amino acid 89 of the encoded protein (E89K). The PNP serum level was 798 nmol/h/mg (normal level 1354 ± 561 nmol/h/mg) 6 weeks after blood transfusion. Hematopoietic stem cell transplantation (HSCT) was planned from a matched unrelated donor; however, she developed an EBV and varicella meningoencephalitis. Atypical malignant cells suggestive of lymphoma were discovered, likely induced by EBV, and suspicious lesions were shown on brain MRI and PET scan. Unfortunately, she passed away before HSCT due to multiorgan failure.


This report emphasizes the challenges in recognizing PNP deficiency in a patient suffering from SLE.

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2


  1. 1.

    Markert ML. Purine nucleoside phosphorylase deficiency. Immunodefic Rev. 1991;3:45–81.

    CAS  PubMed  Google Scholar 

  2. 2.

    Giblett E, Ammann A, Wara D, Sandman R, Diamond L. Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and B-cell immunity. Lancet. 1975;7914:1010–3.

    Google Scholar 

  3. 3.

    Fekrvand S, Yazdani R, Abolhassani H, Ghaffari J, Aghamohammadi A. The first purine nucleoside phosphorylase deficiency patient resembling IgA deficiency and a review of the literature. Immunol Investig. 2019;48(4):410–30.

    CAS  Google Scholar 

  4. 4.

    Shah N, Lingappa L, Konanki R, Rani S, Vedam R, Murugan S. Immunodeficiency, motor delay, and hypouricemia caused by a novel mutation of purine nucleoside phosphorylase gene in an Indian infant. Ann Indian Acad Neurol. 2019;22(2):231–3.

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Arduini A, Marasco E, Marucci G, Pardeo M, Insalaco A, Caiello I, et al. An unusual presentation of purine nucleoside phosphorylase deficiency mimicking systemic juvenile idiopathic arthritis complicated by macrophage activation syndrome. Pediatr Rheumatol Online J. 2019;(1):17, 25.

  6. 6.

    la Marca G, Canessa C, Giocaliere E, Romano F, Malvagia S, Funghini S, et al. Diagnosis of immunodeficiency caused by a purine nucleoside phosphorylase defect by using tandem mass spectrometry on dried blood spots. J Allergy Clin Immunol. 2014;134(1):155–9.

    PubMed  Google Scholar 

  7. 7.

    Cohen A, Grunebaum E, Arpaia E, Roifman C. Immunodeficiency caused by purine nucleoside phosphorylase deficiency. Immunol Allergy Clin N Am. 2000;20:143–59.

    Google Scholar 

  8. 8.

    Kariuki SN, Ghodke-Puranik Y, Dorschner JM, Chrabot BS, Kelly JA, Tsao BP, et al. Genetic analysis of the pathogenic molecular sub-phenotype interferon-alpha identifies multiple novel loci involved in systemic lupus erythematosus. Genes Immun. 2015;16(1):15–23.

    CAS  PubMed  Google Scholar 

  9. 9.

    Cohen A, Gudas A, Ammann A, Staal G, Martin D. Deoxyguanosine triphosphate as a possible toxic metabolite in the immunodeficiency associated with purine nucleoside phosphorylase deficiency. J Clin Invest. 1978;61:1405–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Moallem HJ, Taningo G, Jiang CK, Hirschhorn R, Fikrig S. Purine nucleoside phosphorylase deficiency: a new case report and identification of two novel mutations (Gly156A1a and Val217Ile), only one of which (Gly156A1a) is deleterious. Clin Immunol. 2002;105(1):75–80.

    CAS  PubMed  Google Scholar 

  11. 11.

    Somech R, Lev A, Grisaru-Soen G, Shiran SI, Simon AJ, Grunebaum E. Purine nucleoside phosphorylase deficiency presenting as severe combined immune deficiency. Immunol Res. 2013;56(1):150–4.

    CAS  PubMed  Google Scholar 

  12. 12.

    Rich KC, Arnold WJ, Palella T, Fox IH. Cellular immune deficiency with autoimmune hemolytic anemia in purine nucleoside phosphorylase deficiency. Am J Med. 1979;67(1):172–6.

    CAS  PubMed  Google Scholar 

  13. 13.

    Kiykim A, Simsek I, Kiykim E, Karakoc-Aydiner E, Baris S, Ozen A, et al. Two patients with novel missense mutation in the purine nucleoside phosphorylase gene without serious or recurrent infections. Clin Exp Neuroimmunol. 2016;7:79–82.

  14. 14.

    Simmonds H, Fairbanks L, Morris G, Morgan G, Watson AR, Timms P, et al. Central nervous system dysfunction and erythrocyte guanosine triphosphate depletion in purine nucleoside phosphorylase deficiency. Arch Dis Child. 1987;62(4):385–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Markert ML, Hershfield M, Schiff R, Buckley R. Adenosine deaminase and purine nucleoside phosphorylase deficiencies: evaluation of therapeutic interventions in eight patients. J Clin Immunol. 1987;7(5):389–99.

    CAS  PubMed  Google Scholar 

  16. 16.

    Aust MR, Andrews LG, Barrett MJ, Norby-Slycord CJ, Markert ML. Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency. Am J Hum Genet. 1992;51(4):763–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Dalal I, Grunebaum E, Cohen A, Roifman CM. Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient. Clin Genet. 2001;59(6):430–7.

    CAS  PubMed  Google Scholar 

  18. 18.

    Dror Y, Grunebaum E, Hitzler J, Narendran A, Ye C, Tellier R, et al. Purine nucleoside phosphorylase deficiency associated with a dysplastic marrow morphology. Pediatr Res. 2004;55(3):472–7.

    CAS  PubMed  Google Scholar 

  19. 19.

    Delicou S, Kitra-Roussou V, Peristeri J, Goussetis E, Vessalas G, Rigatou E, et al. Successful HLA-identical hematopoietic stem cell transplantation in a patient with purine nucleoside phosphorylase deficiency. Pediatr Transplant. 2007;11(7):799–803.

    CAS  PubMed  Google Scholar 

  20. 20.

    Parvaneh N, Ashrafi MR, Yeganeh M, Pouladi N, Sayarifar F, Parvaneh L. Progressive multifocal leukoencephalopathy in purine nucleoside phosphorylase deficiency. Brain Dev. 2007;29(2):124–6.

    PubMed  Google Scholar 

  21. 21.

    Parvaneh N, Teimourian S, Jacomelli G, Badalzadeh M, Bertelli M, Zakharova E, et al. Novel mutations of NP in two patients with purine nucleoside phosphorylase deficiency. Clin Biochem. 2008;41(4–5):350–2.

    CAS  PubMed  Google Scholar 

  22. 22.

    Aytekin C, Dogu F, Tanir G, Guloglu D, Santisteban I, Hershfield MS, et al. Purine nucleoside phosphorylase deficiency with fatal course in two sisters. Eur J Pediatr. 2010;169(3):311–4.

    CAS  PubMed  Google Scholar 

  23. 23.

    Walker PL, Corrigan A, Arenas M, Escuredo E, Fairbanks L, Marinaki A. Purine nucleoside phosphorylase deficiency: a mutation update. Nucleosides Nucleotides Nucleic Acids. 2011;30(12):1243–7.

  24. 24.

    Somech R, Lev A, Simon AJ, Hanna S, Etzioni A. T- and B-cell defects in a novel purine nucleoside phosphorylase mutation. J Allergy Clin Immunol. 2012;130(2):539–42.

    CAS  PubMed  Google Scholar 

  25. 25.

    Celmeli F, Turkkahraman D, Uygun V, la Marca G, Hershfield M, Yesilipek A. A successful unrelated peripheral blood stem cell transplantation with reduced intensity-conditioning regimen in a patient with late-onset purine nucleoside phosphorylase deficiency. Pediatr Transplant. 2015;19(2):E47–50.

    PubMed  Google Scholar 

  26. 26.

    Martin J, Sharma R, Nelson RP, Schubert F, Weida J. The first report of a pregnancy in a patient with purine nucleoside phosphorylase deficiency. Fetal Pediatr Pathol. 2016;35(2):120–3.

    CAS  PubMed  Google Scholar 

  27. 27.

    Hanaoka H, Iida H, Kiyokawa T, Takakuwa Y, Kawahata K. A positive direct Coombs test in the absence of hemolytic anemia predicts high disease activity and poor renal response in systemic lupus erythematosus. Lupus. 2018;27(14):2274–8.

    CAS  PubMed  Google Scholar 

  28. 28.

    Ghodke-Puranik Y, Dorschner JM, Vsetecka DM, Amin S, Makol A, Ernste F, et al. Lupus-associated functional polymorphism in PNP causes cell cycle abnormalities and interferon pathway activation in human immune cells. Arthritis Rheumatol. 2017;69(12):2328–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Watson AR, Evans DI, Marsden HB, Miller V, Rogers PA. Purine nucleoside phosphorylase deficiency associated with a fatal lymphoproliferative disorder. Arch Dis Child. 1981;56:563–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Bzowska A, Kulikowska E, Shugar D. Purine nucleoside phosphorylases: properties, functions, and clinical aspects. Pharmacol Ther. 2000;88(3):349–425.

    CAS  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Bandar Al-Saud.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Al-Saud, B., Al Alawi, Z., Hussain, F.B. et al. A Case with Purine Nucleoside Phosphorylase Deficiency Suffering from Late-Onset Systemic Lupus Erythematosus and Lymphoma. J Clin Immunol 40, 833–839 (2020). https://doi.org/10.1007/s10875-020-00800-y

Download citation


  • PNP
  • severe combined immunodeficiency
  • systemic lupus erythematosus
  • Epstein-Barr virus
  • CNS lymphoma