Abstract
PNP deficiency is an autosomal recessive metabolic disorder characterized by severe combined immunodeficiency and by complex neurological symptomatology including ataxia, developmental delay and spasticity. Patients usually die in the first or second decade of life due to recurrent infections. The only curative treatment is bone marrow transplantation (BMT). We describe a 22-month-old girl who underwent BMT from her HLA-identical brother. Conditioning consisted of busulfan and fludarabine only, resulting in low toxicity and prompt engraftment. At 18 months after BMT, the girl has developed normal immunological functions, and her neurological status has improved. Bone Marrow Transplantation (2001) 28, 93–96.
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References
Markert ML . Purine nucleoside phosphorylase deficiency Immunodefic Rev 1991 3: 45–81
Simmonds HA . Diagnosis and treatment of inborn errors of purine and pyrimidine metabolism: an overview Adv Exp Med Biol 1994 370: 1–6
Hirschhorn R . Inherited enzyme deficiencies and immunodeficiency: adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiencies Clin Immunol Immunopathol 1986 40: 157–165
Giblett ER . ADA and PNP deficiencies: how it all began Ann N Y Acad Sci 1985 451: 1–8
Simmonds HA, Duley JA, Fairbanks LD, McBride MB . When to investigate for purine and pyrimidine disorders. Introduction and review of clinical and laboratory indications J Inherit Metab Dis 1997 20: 214–226
Gangi-Peterson L, Sorscher DH et al. Nucleotide pool imbalance and adenosine deaminase deficiency induce alterations of N-region insertions during V(D)J recombination J Clin Invest 1999 103: 833–841
Pannicke U, Tuchschmid P, Friedrich W et al. 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 1996 98: 706–709
Aust MR, Andrews LG, Barrett MJ et al. Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency Am J Hum Genet 1992 51: 763–772
Andrews LG, Markert ML . Exon skipping in purine nucleoside phosphorylase mRNA processing leading to severe immunodeficiency J Biol Chem 1992 267: 7834–7838
Sasaki Y, Iseki M, Yamaguchi S et al. Direct evidence of autosomal recessive inheritance of Arg24 to termination codon in purine nucleoside phosphorylase gene in a family with a severe combined immunodeficiency patient Hum Genet 1998 103: 81–85
Ortin M, Rhymes H, Weightman H, Darbyshire PJ . Unrelated-donor bone marrow transplantation in the treatment of purine nucleoside phosphorylase deficiency Bone Marrow Transplant 2000 25: (Suppl. 1) 112
Hallett RJ, Gaspar B, Duley JA et al. Allogeneic bone marrow transplantation corrects the immunodeficiency in PNP deficiency but does not reverse the neurological abnormalities Cell Mol Biol Lett 1999 4: 374
Carpenter PA, Ziegler JB, Vowels MR . Late diagnosis and correction of purine nucleoside phosphorylase deficiency with allogeneic bone marrow transplantation Bone Marrow Transplant 1996 17: 121–124
Seidemann K, Tiemann M, Henze G et al. Therapy for non-Hodgkin lymphoma in children with primary immunodeficiency: analysis of 19 patients from the BFM trials Med Pediatr Oncol 1999 33: 536–544
Nelson DM, Butters KA, Markert ML et al. Correction of proliferative responses in purine nucleoside phosphorylase (PNP)-deficient T lymphocytes by retroviral-mediated PNP gene transfer and expression J Immunol 1995 15: 3006–3014
Wolff JA, Friedmann T . Approaches to gene therapy in disorders of purine metabolism Rheum Dis Clin North Am 1988 14: 459–477
Hassan M, Ljungman P, Ringden O et al. The effect of busulphan on the pharmacokinetics of cyclophosphamide and its 4-hydroxy metabolite: time interval influence on therapeutic efficacy and therapy-related toxicity Bone Marrow Transplant 2000 25: 915–924
Kapelushnik J, Or R, Slavin S, Nagler A . A fludarabine-based protocol for bone marrow transplantation in Fanconi's anemia Bone Marrow Transplant 1997 20: 1109–1110
Slavin S, Nagler A, Naparstek E et al. Nonmyeloablative stem cell transplantation and cell therapy as an alternative to conventional bone marrow transplantation with lethal cytoreduction for the treatment of malignant and nonmalignant hematologic diseases Blood 1998 91: 756–763
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HAS is indebted to EC grant BMH4-CT98–3079.
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Classen, C., Schulz, A., Sigl-Kraetzig, M. et al. Successful HLA-identical bone marrow transplantation in a patient with PNP deficiency using busulfan and fludarabine for conditioning. Bone Marrow Transplant 28, 93–96 (2001). https://doi.org/10.1038/sj.bmt.1703100
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DOI: https://doi.org/10.1038/sj.bmt.1703100
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