title: 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.
abstract: Purine nucleoside phosphorylase (PNP) is an enzyme active in the purine salvage pathway. PNP deficiency caused by autosomal recessive mutations in the PNP gene leads to severe combined immunodeficiency (SCID) and in two thirds of cases also to neurological effects such as developmental delay, ataxia, and motor impairment.PNP deficiency has a poor outcome, and the only curative treatment is allogenic hematopoietic stem cell transplantation (HSCT). We present the first Swedish patient with PNP deficiency with novel mutations in the PNP gene and the immunological results of the HSCT and evaluate the impact of HSCT on the neurological symptoms. The patient presented early in life with neurological symptoms and suffered later from repeated serious respiratory tract infections. Biochemical tests showed severe reduction in PNP activity (1% residual activity). Genetic testing revealed two new mutations in the PNP gene: c.729C>G (p.Asn243Lys) and c.746A>C (p.Tyr249Cys). HSCT was performed with an unrelated donor, resulting in prompt and sustained engraftment and complete donor chimerism. There was no further aggravation of the patient's neurological symptoms at 21 months post HSCT, and appropriate developmental milestones were achieved. HSCT is curative for the immunological defect caused by PNP deficiency, and our case strengthens earlier reports that HSCT is effective as a treatment even for neurological symptoms in PNP deficiency.
authors.affiliation: Childrens Hospital, Skåne University Hospital, Lasarettsgatan 48, SE-221 85, Lund, Sweden. nicholas.brodszki@skane.se.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Brodszki
authors.affiliation: Lund University, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Svensson
authors.affiliation: Academic Medical Center Lab. Genetic Metabolic Diseases, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: André B P
authors.initials: AB
authors.lastname: van Kuilenburg
authors.affiliation: Academic Medical Center Lab. Genetic Metabolic Diseases, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Judith
authors.initials: J
authors.lastname: Meijer
authors.affiliation: Academic Medical Center Lab. Genetic Metabolic Diseases, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Lida
authors.initials: L
authors.lastname: Zoetekouw
authors.affiliation: Department of Laboratory Medicine, Section of Microbiology, Immunology and Glycobiology, Lund University, Lund, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Truedsson
authors.affiliation: Childrens Hospital, Skåne University Hospital, Lasarettsgatan 48, SE-221 85, Lund, Sweden.
authors.forename: Jacek
authors.initials: J
authors.lastname: Toporski
keywords: Developmental delay; Hematopoietic stem cell transplantation; Immunodeficiency; Lymphocytes; Matched unrelated donor; Pediatric; Purine nucleoside phosphorylase