nach oben

Journal of Clinical Immunology

Erschienen in:

09.11.2019 | Original Article

The Broad Clinical Spectrum and Transplant Results of PNP Deficiency

Erschienen in: Journal of Clinical Immunology | Ausgabe 1/2020

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Purine nucleoside phosphorylase (PNP) is a known yet rare cause of combined immunodeficiency with a heterogeneous clinical presentation. We aim to add to the expanding clinical spectrum of disease, and to summarize the available data on bone marrow transplant for this condition.

Methods

Data was collected from patient files retrospectively. A review of the literature of hematopoietic stem cell transplantation (HSCT) for PNP deficiency was conducted.

Results

Four patients were treated in two centers in Israel. One patient died of EBV-related lymphoma with CNS involvement prior to transplant. The other three patients underwent successful HSCT with good immune reconstitution post-transplant (follow-up 8–108 months) and excellent neurological outcomes.

Conclusion

PNP is a variable immunodeficiency and should be considered in various clinical contexts, with or without neurological manifestations. HSCT offers a good treatment option, with excellent clinical outcomes, when preformed in a timely manner.

Madkaikar MR, Kulkarni S, Utage P, Fairbanks L, Ghosh K, Marinaki A, et al. Purine nucleoside phosphorylase deficiency with a novel PNP gene mutation: a first case report from India. BMJ Case Rep [Internet]. 2011;2011:bcr0920114804–bcr0920114804. [cited 2019 Aug 24]. Available from: http://casereports.bmj.com/cgi/doi/10.1136/bcr.09.2011.4804

Myers LA, Hershfield MS, Neale WT, Escolar M, Kurtzberg J. Purine nucleoside phosphorylase deficiency (PNP-def) presenting with lymphopenia and developmental delay: successful correction with umbilical cord blood transplantation. J Pediatr [Internet]. 2004;145:710–2. [cited 2019 Feb 25]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15520787

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 [Internet]. 2012. p. 39–42. [cited 2019 Feb 25]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23430937

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 [Internet]. 2013;56:150–4. [cited 2019 Aug 24]. Available from: http://link.springer.com/10.1007/s12026-012-8380-9

Alangari A, Al-Harbi A, Al-Ghonaium A, Santisteban I, Hershfield M. Purine nucleoside phosphorylase deficiency in two unrelated Saudi patients. Ann Saudi Med [Internet] 2019;29:309–12. [cited 2019 Apr 23]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19584574

Aytekin C, Yuksek M, Dogu F, Yagmurlu A, Yildiran A, Fitoz S, et al. An unconditioned bone marrow transplantation in a child with purine nucleoside phosphorylase deficiency and its unique complication. Pediatr Transplant [Internet]. 2008;12:479–82. [cited 2019 Aug 24]. Available from: http://doi.wiley.com/10.1111/j.1399-3046.2007.00890.x

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 [Internet]. 1996;128:373–6. [cited 2019 Apr 23]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8774508

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 [Internet]. 2015;19:E47-50. [cited 2019 Aug 24]. Available from: http://doi.wiley.com/10.1111/petr.12413

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 [Internet]. 2010;169:311–4. [cited 2019 Aug 24]. Available from: http://link.springer.com/10.1007/s00431-009-1029-6

10.

Yeates L, Slatter MA, Gennery AR. Infusion of sibling marrow in a patient with purine nucleoside phosphorylase deficiency leads to split mixed donor chimerism and normal immunity. Front Pediatr [Internet]. 2017;5:143. [cited 2019 Aug 24]. Available from: http://journal.frontiersin.org/article/10.3389/fped.2017.00143/full

11.

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 [Internet]. 2004;55:472–7. [cited 2019 Aug 24]. Available from: http://www.nature.com/doifinder/10.1203/01.PDR.0000111286.23110.F8

12.

Dalal I, Grunebaum E, Cohen A, Roifman CM. Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient. Clin Genet [Internet]. 2001;59:430–7. [cited 2019 Apr 29]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11453975

13.

Gelfand EW, Dosch HM, Biggar WD, Fox IH. Partial purine nucleoside phosphorylase deficiency. Studies of lymphocyte function. J Clin Invest [Internet]. 1978;61:1071–80. [cited 2019 Apr 29]. Available from: http://www.jci.org/articles/view/109006

14.

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 [Internet]. 2002;105:75–80. [cited 2019 Feb 25]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12483996

15.

Baguette C, Vermylen C, Brichard B, Louis J, Dahan K, Vincent MF, et al. Persistent developmental delay despite successful bone marrow transplantation for purine nucleoside phosphorylase deficiency. J Pediatr Hematol Oncol [Internet]. 2002;24:69–71. [cited 2019 Feb 25]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11902746

16.

Brodszki N, Svensson M, van Kuilenburg ABP, Meijer J, Zoetekouw L, Truedsson L, et al. 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 [Internet]. 2015;24:83–9. [cited 2019 Aug 24]. Available from: http://link.springer.com/10.1007/8904_2015_444

17.

Dehkordy SF, Aghamohammadi A, Ochs HD, Rezaei N. Primary immunodeficiency diseases associated with neurologic manifestations. J Clin Immunol [Internet]. 2012;32:1–24. [cited 2019 Aug 24]. Available from: http://link.springer.com/10.1007/s10875-011-9593-8

18.

Classen CF, Schulz AS, Sigl-Kraetzig M, Hoffmann GF, Simmonds HA, Fairbanks L, et al. Successful HLA-identical bone marrow transplantation in a patient with PNP deficiency using busulfan and fludarabine for conditioning. Bone Marrow Transplant [Internet]. 2001;28:93–6. [cited 2019 Apr 29]. Available from: http://www.nature.com/articles/1703100

19.

Carson DA, Lakow E, Wasson DB, Kamatani N. Lymphocyte dysfunction caused by deficiencies in purine metabolism. Immunol Today [Internet]. 1981;2:234–8. [cited 2019 Apr 1]. Available from: https://linkinghub.elsevier.com/retrieve/pii/0167569981900104

20.

Ullman B, Gudas LJ, Clift SM, Martin DW. Isolation and characterization of purine-nucleoside phosphorylase-deficient T-lymphoma cells and secondary mutants with altered ribonucleotide reductase: genetic model for immunodeficiency disease. Proc Natl Acad Sci U S A [Internet]. 1979;76:1074–8. [cited 2019 Apr 1]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/108675

21.

Arpaia E, Benveniste P, Di Cristofano A, Gu Y, Dalal I, Kelly S, et al. Mitochondrial basis for immune deficiency. Evidence from purine nucleoside phosphorylase-deficient mice. J Exp Med [Internet]. 2000;191:2197–208. [cited 2019 Feb 25]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10859343

22.

Papinazath T, Min W, Sujiththa S, Cohen A. Effects of purine nucleoside phosphorylase deficiency on thymocyte development. J Allergy Clin Immunol [Internet]. 2011;128:854-63 https://doi.org/10.1016/j.jaci.2011.07.039

23.

Simmonds HA, Fairbanks LD, Morris GS, 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 [Internet]. 1987;62:385–91. [cited 2019 Apr 23]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2439024

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 [Internet]. 2012;130:539–42. [cited 2019 Apr 30]. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0091674912006033

25.

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 [Internet]. 2007;11:799–803. [cited 2019 Aug 24]. Available from: http://doi.wiley.com/10.1111/j.1399-3046.2007.00772.x

26.

Pannicke U, Tuchschmid P, Friedrich W, Bartram CR, \. Two novel missense and frameshift mutations in exons 5 and 6 of the purine nucleoside phosphorylase (PNP) gene in a severe combined immunodeficiency (SCID) patient. Hum Genet [Internet]. 1996;98:706–9. [cited 2019 May 6]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8931706

27.

Isoyama K, Ohnuma K, Ikuta K, Toyoda Y, Nakajima F, Yamada K, et al. Unrelated cord blood transplantation for second hemopoietic stem cell transplantation. Pediatr Int [Internet]. 2003;45:268–74. [cited 2019 May 7]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12828579

28.

Al-saud B, Alsmadi O, Al-muhsen S, Al-ghonaium A, Al-dhekri H. Case Report A novel mutation in purine nucleoside phosphorylase in a child with normal uric acid levels. Clin Biochem [Internet]. The Canadian Society of Clinical Chemists; 2009;42:1725–7. Available from: https://doi.org/10.1016/j.clinbiochem.2009.08.017

29.

Worth AJJ, Houldcroft CJ, Booth C. Severe Epstein-Barr virus infection in primary immunodeficiency and the normal host. Br J Haematol [Internet]. 2016;175:559–76. [cited 2019 May 27]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27748521

30.

Shabani M, Nichols KE, Rezaei N. Primary immunodeficiencies associated with EBV-induced lymphoproliferative disorders. Crit Rev Oncol Hematol [Internet]. 2016;108:109–27. [cited 2019 May 27] Available from: http://www.ncbi.nlm.nih.gov/pubmed/27931829

31.

Cohen JI. Primary immunodeficiencies associated with EBV disease. Curr Top Microbiol Immunol [Internet]. 2015. p. 241–65. [cited 2019 May 27]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26424649

32.

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 [Internet]. 2014;134:155–9. [cited 2019 Aug 24]. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0091674914002656

33.

Pai S-Y, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, et al. Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N Engl J Med [Internet]. 2014;371:434–46. [cited 2019 Jul 8]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/25075835

34.

Mansouri A, Min W, Cole CJ, Josselyn SA, Henderson JT, van Eede M, et al. Cerebellar abnormalities in purine nucleoside phosphorylase deficient mice. Neurobiol Dis [Internet]. 2012;47:201–9. [cited 2019 Aug 24]. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0969996112001301

Titel: The Broad Clinical Spectrum and Transplant Results of PNP Deficiency
Publikationsdatum: 09.11.2019
Erschienen in: Journal of Clinical Immunology / Ausgabe 1/2020
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-019-00698-1

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

25.04.2024 | Hypotonie | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

The Broad Clinical Spectrum and Transplant Results of PNP Deficiency

Abstract

Purpose

Methods

Results

Conclusion

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Viel Bewegung in der Parkinsonforschung

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Innere Medizin

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2020

How I Manage Natural Killer Cell Deficiency

Novel Missense Mutation in SP110 Associated with Combined Immunodeficiency and Advanced Liver Disease Without VOD

TTC7A Variants Previously Described to Cause Enteropathy Are Observed on a Single Haplotype and Appear Non-pathogenic in Pediatric Inflammatory Bowel Disease Patients

Immune Dysregulation in the Tonsillar Microenvironment of Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA) Syndrome

A Large Cohort of RAG1/2-Deficient SCID Patients—Clinical, Immunological, and Prognostic Analysis

A New Patient with Inherited TYK2 Deficiency

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

Viel Bewegung in der Parkinsonforschung

Adjuvante Immuntherapie verlängert Leben bei RCC

Update Innere Medizin