title: Purine nucleoside phosphorylase deficiency associated with a dysplastic marrow morphology.
abstract: Purine nucleoside phosphorylase (PNP) deficiency is an autosomal recessive metabolic disorder characterized by severe combined immunodeficiency and by complex neurologic symptomatology including ataxia, developmental delay, and spasticity. Herein we report severe marrow dysplasia in a patient with PNP deficiency. Drug-related marrow dysfunction was unlikely, and marrow virological studies were negative. A preleukemic myelodysplastic syndrome was also unlikely due to normal marrow CD34+ cells, colony growth in clonogenic assay of marrow mononuclear cells, apoptosis rate, and Fas expression on marrow nucleated cells, as well as morphologic improvement of the marrow dysplasia after normal red blood cell transfusion. The patient's marrow stroma showed hypersensitivity to irradiation and undetectable PNP enzyme activity similar to peripheral lymphocytes. This is the first report of PNP deficiency associated with increased lymphocyte and marrow stromal sensitivity to irradiation. We conclude that marrows from patients with PNP deficiency might have hypersensitivity to irradiation and can develop dysplastic morphology, caused either directly or indirectly by the inherited enzymatic defect.
authors.affiliation: Division of Immunology and Allergy, The Hospital for Sick Children, 555 University Ave., Rm. 7279 Elm Wing, Toronto, Ontario, M5G 1X8, Canada. chaim.roifman@sickkids.ca
authors.forename: Yigal
authors.initials: Y
authors.lastname: Dror
authors.forename: Eyal
authors.initials: E
authors.lastname: Grunebaum
authors.forename: Johann
authors.initials: J
authors.lastname: Hitzler
authors.forename: Aru
authors.initials: A
authors.lastname: Narendran
authors.forename: Charles
authors.initials: C
authors.lastname: Ye
authors.forename: Raymond
authors.initials: R
authors.lastname: Tellier
authors.forename: Vernon
authors.initials: V
authors.lastname: Edwards
authors.forename: Melvin H
authors.initials: MH
authors.lastname: Freedman
authors.forename: Chaim M
authors.initials: CM
authors.lastname: Roifman
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D001855:Bone Marrow Diseases / Q000201:enzymology*; D002675:Child, Preschool; D017931:DNA Primers; D006801:Humans; D008297:Male; D008854:Microscopy, Electron; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency* / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D017931:DNA Primers; D019014:fas Receptor; D011683:Purine-Nucleoside Phosphorylase