Progressive Hypotonia with Lymphopenia

  • Mihaela Tatiana Bataneant
  • Patricia Urtila


  • T cell lymphopenia, and neurologic findings with fluctuation and deterioration over time should raise the suspicion of purine nucleoside phosphorylase (PNP) deficiency

  • Very low serum uric acid level is in favor of PNP deficiency but a normal level does not exclude PNP deficiency

  • The diagnosis is established by measurement of PNP enzyme activity in red cells or blood mononuclear cells. Elevated serum or urinary levels of inosine and guanosine is also confirmatory

  • The only available cure for PNP deficiency is HSCT


Purine nucleoside phosphorylase Lymphopenia Serum uric acid 


  1. 1.
    Katirji B, Kaminski H, Preston D. Spinal muscular atrophies. neuromuscular disorders in clinical practice. Boston: Butterworth-Heinemann; 2002. p. 445–53.Google Scholar
  2. 2.
    Yuzbasiyan-Gurkan V, Grider A, Nostrant T, Cousins RJ, Brewer GJ. Treatment of Wilson’s disease with zinc: X. Intestinal metallothionein induction. J Lab Clin Med. 1992;120(3):380–6.PubMedGoogle Scholar
  3. 3.
    Dubowitz V. Muscle disorders in childhood. 2nd ed. Philadelphia: WB Saunder; 1995. p. 34–132.Google Scholar
  4. 4.
    Roifman CM, Somech R, Kavadas F, Pires L, Nahum A, Dalal I, Grunebaum E. Defining combined immunodeficiency. J Allergy Clin Immunol. 2012;130(1):177–83.CrossRefGoogle Scholar
  5. 5.
    Buckley RH, Schiff RI, Schiff SE, Markert ML, Williams LW, Harville TO, Roberts JL, Puck JM. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. 1997;130(3):378–87.CrossRefGoogle Scholar
  6. 6.
    Subbarayan A, Colarusso G, Hughes SM, Gennery AR, Slatter M, Cant AJ, Arkwright PD. Clinical features that identify children with primary immunodeficiency diseases. Pediatrics. 2011;127(5):810–6.CrossRefGoogle Scholar
  7. 7.
    Arkwright PD, Gennery AR. Ten warning signs of primary immunodeficiency: a new paradigm is needed for the 21st century. Ann N Y Acad Sci. 2011;1238:7–14.CrossRefGoogle Scholar
  8. 8.
    Felgentreff K, Perez-Becker R, Speckmann C, Schwarz K, Kalwak K, Markelj G, Avcin T, Qasim W, Davies EG, Niehues T, Ehl S. Clinical and immunological manifestations of patients with atypical severe combined immunodeficiency. Clin Immunol (Orlando, Fla). 2011;141(1):73–82.CrossRefGoogle Scholar
  9. 9.
    Saudubray J, Baumgartner M, Walter J. Inborn metabolic diseases-diagnosis and treatment. Berlin: Springer; 2016.CrossRefGoogle Scholar
  10. 10.
    Alangari A, Al-Harbi A, Al-Ghonaium A, Santisteban I, Hershfield M. Purine nucleoside phosphorylase deficiency in two unrelated Saudi patients. Ann Saudi Med. 2009;29(4):309–12.CrossRefGoogle Scholar
  11. 11.
    Edwards NL. Immunodeficiencies associated with errors in purine metabolism. Med Clin North Am. 1985;69(3):505–18.CrossRefGoogle Scholar
  12. 12.
    Dror Y, Grunebaum E, Hitzler J, Narendran A, Ye C, Tellier R, Edwards V, Freedman MH, Roifman CM. Purine nucleoside phosphorylase deficiency associated with a dysplastic marrow morphology. Pediatr Res. 2004;55(3):472–7.CrossRefGoogle Scholar
  13. 13.
    Soutar RL, Day RE. Dysequilibrium/ataxic diplegia with immunodeficiency. Arch Dis Child. 1991;66(8):982–3.CrossRefGoogle Scholar
  14. 14.
    Albuquerque W, Gaspar HB. Bilateral sensorineural deafness in adenosine deaminase-deficient severe combined immunodeficiency. J Pediatr. 2004;144(2):278–80.CrossRefGoogle Scholar
  15. 15.
    Cederbaum SD, Kaitila I, Rimoin DL, Stiehm ER. The chondro-osseous dysplasia of adenosine deaminase deficiency with severe combined immunodeficiency. J Pediatr. 1976;89(5):737–42.CrossRefGoogle Scholar
  16. 16.
    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.CrossRefGoogle Scholar
  17. 17.
    Markert M. Purine nucleoside phosphorylase deficiency. Immunodefic Rev. 1991;3(1):45–81.PubMedGoogle Scholar
  18. 18.
    Hallett R, Cronin S, Morgan G. Normal uric acid concentrations in a purine nucleoside phosphorylase (PNP) deficient child presenting with severe chicken pox, possible immunodeficiency and developmental delay. Adv Exp Med Biol. 1994;370:387–9.CrossRefGoogle Scholar
  19. 19.
    Delicou S, Kitra-Roussou V, Peristeri J, Goussetis E, Vessalas G, Rigatou E, Psychou F, Salavoura K, Grafakos S. Successful HLA-identical hematopoietic stem cell transplantation in a patient with purine nucleoside phosphorylase deficiency. Pediatr Transplant. 2007;11(7):799–803.CrossRefGoogle Scholar
  20. 20.
    Delicou S, Kitra-Roussou V, Peristeri J. Successful HLA-identical hematopoietic stem cell transplantation in a patient with purine nucleoside phosphorylase deficiency. Pediatr Transplant. 2007;11(7):799–803.CrossRefGoogle Scholar
  21. 21.
    Myers L, Hershfield M, Neale W. Purine nucleoside phosphorylase deficiency (PNP-def) presenting with lymphopenia and developmental delay: successful correction with umbilical cord blood transplantation. J Pediatr. 2004;145:710–2.CrossRefGoogle Scholar
  22. 22.
    Singh V. Cross correction following haemopoietic stem cell transplant for purine nucleoside phosphorylase deficiency: engrafted donor-derived white blood cells provide enzyme to residual enzyme-deficient recipient cells. JIMD Rep. 2012;6:39–42.CrossRefGoogle Scholar
  23. 23.
    Brodszki N, Svensson M, van Kuilenburg AB, Meijer J, Zoetekouw L, Truedsson L, Toporski J. Novel genetic mutations in the first Swedish patient with purine nucleoside phosphorylase deficiency and clinical outcome after hematopoietic stem cell transplantation with HLA-matched unrelated donor. JIMD Rep. 2015;24:83–9.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Mihaela Tatiana Bataneant
    • 1
    • 2
  • Patricia Urtila
    • 1
    • 2
  1. 1.University of Medicine and Pharmacy “Victor Babes” TimisoaraTimisoaraRomania
  2. 2.“Louis Turcanu” Children’s Emergency Clinical HospitalTimisoaraRomania

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