Abstract
Purine nucleoside phosphorylase (PNP) deficiency is an autosomal recessive genetic disorder of the purine salvage pathway, associated with a variable extent of immunodeficiency. Here, we report a PNP-deficient patient who presented early in life with clinical and laboratory characteristics of severe combined immunodeficiency, including severe infections, marked T-and B-cell deficiency, lack of lymphocyte response to mitogenic stimulation, monoclonal T-cell receptors representation and the absence of T-cell receptor excision circles and Kappa-receptor excision circles. The patient carried homozygote mutation at the PNP gene that putatively led to aberrant splicing, allowing normal and abnormally spliced products from the mutant alleles. We suggest that the aberrant slice site was used preferentially over the normal slice site in some cells correlating with the severity of disease.
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Roifman CM, Somech R, Kavadas F, Pires L, Nahum A, Dalal I, Grunebaum E. Defining combined immunodeficiency. J Allergy Clin Immunol. 2012;130:177–83.
Borte S, von Döbeln U, Fasth A, Wang N, Janzi M, Winiarski J, Sack U, Pan-Hammarström Q, Borte M, Hammarström L. Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR. Blood. 2012;119:2552–5.
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;51:763–72.
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;55:472–7.
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;130:539–42.
Markert ML. Purine nucleoside phosphorylase deficiency. Immunodefic Rev. 1991;3(1):45–81.
Lev A, Simon AJ, Bareket M, Bielorai B, Hutt D, Amariglio N, Rechavi G, Somech R. The kinetics of early T and B cell immune recovery after bone marrow transplantation in RAG-2-deficient SCID patients. PLoS ONE. 2012;7(1):e30494.
Dalal I, Grunebaum E, Cohen A, Roifman CM. Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient. Clin Genet. 2001;59:430–7.
Parvaneh N, Teimourian S, Jacomelli G, Badalzadeh M, Bertelli M, Zakharova E, Tabatabaei P, Parvaneh L, Pourakbari B, Yeganeh M, Tamizifar B, Mamishi S, Micheli V. Novel mutations of NP in two patients with purine nucleoside phosphorylase deficiency. Clin Biochem. 2008;41:350–2.
Micheli V, Camici M, Tozzi MG, Ipata PL, Sestini S, Bertelli M, Pompucci G. Neurological disorders of purine and pyrimidine metabolism. Curr Top Med Chem. 2011;11:923–47.
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;105:75–80.
Al-Saud B, Alsmadi O, Al-Muhsen S, Al-Ghonaium A, Al-Dhekri H, Arnaout R, Hershfield MS, Al-Mousa H. A novel mutation in purine nucleoside phosphorylase in a child with normal uric acid levels. Clin Biochem. 2009;42:1725–7.
Tam DA Jr, Leshner RT. Stroke in purine nucleoside phosphorylase deficiency. Pediatr Neurol. 1995;12:146–8.
Parvaneh N, Ashrafi MR, Yeganeh M, Pouladi N, Sayarifar F, Parvaneh L. Progressive multifocal leukoencephalopathy in purine nucleoside phosphorylase deficiency. Brain Dev. 2007;29:124–6.
Tabarki B, Yacoub M, Tlili K, Trabelsi A, Dogui M, Essoussi AS. Familial spastic paraplegia as the presenting manifestation in patients with purine nucleoside phosphorylase deficiency. J Child Neurol. 2003;18:140–1.
Mansouri A, Min W, Cole CJ, Josselyn SA, Henderson JT, van Eede M, Henkelman RM, Ackerley C, Grunebaum E, Roifman CM. Cerebellar abnormalities in purine nucleoside phosphorylase deficient mice. Neurobiol Dis. 2012;47:201–9.
Walker PL, Corrigan A, Arenas M, Escuredo E, Fairbanks L, Marinaki A. Purine nucleoside phosphorylase deficiency: a mutation update. Nucleosides, Nucleotides Nucleic Acids. 2011;30:1243–7.
Markert ML, Finkel BD, McLaughlin TM, Watson TJ, Collard HR, McMahon CP, Andrews LG, Barrett MJ, Ward FE. Mutations in purine nucleoside phosphorylase deficiency. Hum Mutat. 1997;9:118–21.
Broome CB, Graham ML, Saulsbury FT, Hershfield MS, Buckley RH. Correction of purine nucleoside phosphorylase deficiency by transplantation of allogeneic bone marrow from a sibling. J Pediatr. 1996;128(3):373–6.
Acknowledgments
The Jeffery Modell Foundation (JMF), the Legacy Heritage Biomedical Science Partnership Program of the Israel Science Foundation and the Chief Scientist Office of the Ministry of Health, for their support.
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The authors declare that they have no conflict of interest.
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Somech, R., Lev, A., Grisaru-Soen, G. et al. Purine nucleoside phosphorylase deficiency presenting as severe combined immune deficiency. Immunol Res 56, 150–154 (2013). https://doi.org/10.1007/s12026-012-8380-9
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DOI: https://doi.org/10.1007/s12026-012-8380-9