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.
(2015) In JIMD Reports 24. p.9-83- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5453327
- author
- Brodszki, Nicholas LU ; Svensson, Maria LU ; van Kuilenburg, André B P ; Meijer, Judith ; Zoetekouw, Lida ; Truedsson, Lennart LU and Toporski, Jacek LU
- organization
- publishing date
- 2015-05-13
- type
- Contribution to journal
- publication status
- published
- subject
- in
- JIMD Reports
- volume
- 24
- pages
- 7 pages
- publisher
- Springer
- external identifiers
-
- pmid:25967230
- scopus:84956540066
- pmid:25967230
- ISSN
- 2192-8304
- DOI
- 10.1007/8904_2015_444
- language
- English
- LU publication?
- yes
- id
- 10d8c009-bbb4-4e32-b585-3e139dee5c41 (old id 5453327)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25967230?dopt=Abstract
- date added to LUP
- 2016-04-04 09:39:57
- date last changed
- 2022-02-13 18:25:38
@article{10d8c009-bbb4-4e32-b585-3e139dee5c41,
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.}},
author = {{Brodszki, Nicholas and Svensson, Maria and van Kuilenburg, André B P and Meijer, Judith and Zoetekouw, Lida and Truedsson, Lennart and Toporski, Jacek}},
issn = {{2192-8304}},
language = {{eng}},
month = {{05}},
pages = {{9--83}},
publisher = {{Springer}},
series = {{JIMD Reports}},
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.}},
url = {{http://dx.doi.org/10.1007/8904_2015_444}},
doi = {{10.1007/8904_2015_444}},
volume = {{24}},
year = {{2015}},
}