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

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Abstract

Background

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.

Methods

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.

Conclusion

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

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References

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

    PubMed  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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. 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. 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.

    Article  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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. 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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  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.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Section of Allergy and Immunology, Department of Pediatrics, Division of Allergy & Immunology, King Faisal Specialist Hospital & Research Center, P.O. Box 3354, MBC-58, Riyadh, 11211, Saudi Arabia

    Bandar Al-Saud & Zainab Al Alawi

  2. College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

    Bandar Al-Saud & Sulaiman M. Al-Mayouf

  3. Department of Pediatrics, College of Medicine, King Faisal University, Alhasa, Saudi Arabia

    Zainab Al Alawi

  4. Department of Radiology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia

    Faisal Bin Hussain

  5. Department of Medicine, Duke University Medical Center, Durham, NC, USA

    Michael Hershfield

  6. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

    Fowzan S. Alkuraya

  7. Department of Pediatrics, Division of Rheumatology, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia

    Sulaiman M. Al-Mayouf

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  1. Bandar Al-Saud
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  2. Zainab Al Alawi
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  3. Faisal Bin Hussain
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Correspondence to Bandar Al-Saud.

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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

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  • DOI: https://doi.org/10.1007/s10875-020-00800-y

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