Purine nucleoside phosphorylase deficiency presenting as severe combined immune deficiency

Raz Somech; Atar Lev; Galia Grisaru-Soen; Shelly I Shiran; Amos J Simon; Eyal Grunebaum

doi:10.1007/s12026-012-8380-9

Purine nucleoside phosphorylase deficiency presenting as severe combined immune deficiency

Immunol Res. 2013 May;56(1):150-4. doi: 10.1007/s12026-012-8380-9.

Authors

Raz Somech¹, Atar Lev, Galia Grisaru-Soen, Shelly I Shiran, Amos J Simon, Eyal Grunebaum

Affiliation

¹ Cancer Research Center, Pediatric Department, Pediatric Immunology Service, Jeffery Modell Foundation (JMF) Center, Edmond and Lily Safra Children's Hospital, Tel Aviv University, Tel Aviv, Israel. rsomech@hotmail.com

PMID: 23371835
DOI: 10.1007/s12026-012-8380-9

Abstract

Purine nucleoside phosphorylase (PNP) deficiency is an autosomal recessive genetic disorder of the purine salvage pathway, associated with a variable extent of immunodeficiency. Here, we report a PNP-deficient patient who presented early in life with clinical and laboratory characteristics of severe combined immunodeficiency, including severe infections, marked T-and B-cell deficiency, lack of lymphocyte response to mitogenic stimulation, monoclonal T-cell receptors representation and the absence of T-cell receptor excision circles and Kappa-receptor excision circles. The patient carried homozygote mutation at the PNP gene that putatively led to aberrant splicing, allowing normal and abnormally spliced products from the mutant alleles. We suggest that the aberrant slice site was used preferentially over the normal slice site in some cells correlating with the severity of disease.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

B-Lymphocytes / immunology*
B-Lymphocytes / pathology
C-Reactive Protein / metabolism
Candidiasis, Oral / etiology
Consanguinity
DNA Mutational Analysis
Diagnosis, Differential
Female
Humans
Infant
Lymph Nodes / immunology
Lymphocyte Activation
Mutation / genetics
Palatine Tonsil / immunology
Primary Immunodeficiency Diseases
Protein Splicing / genetics
Purine-Nucleoside Phosphorylase / deficiency*
Purine-Nucleoside Phosphorylase / genetics
Purine-Nucleoside Phosphorylase / immunology
Purine-Nucleoside Phosphorylase / metabolism*
Purine-Pyrimidine Metabolism, Inborn Errors / diagnosis*
Purine-Pyrimidine Metabolism, Inborn Errors / genetics
Purine-Pyrimidine Metabolism, Inborn Errors / immunology
Receptors, Antigen, T-Cell / genetics
Respiratory Distress Syndrome / etiology
Severe Combined Immunodeficiency / diagnosis*
T-Lymphocytes / immunology*
T-Lymphocytes / pathology

Substances

Receptors, Antigen, T-Cell
C-Reactive Protein
Purine-Nucleoside Phosphorylase

Supplementary concepts

Purine Nucleoside Phosphorylase Deficiency