Toggle Main Menu Toggle Search

Open Access padlockePrints

Diagnosis of immunodeficiency caused by a purine nucleoside phosphorylase defect by using tandem mass spectrometry on dried blood spots

Lookup NU author(s): Professor Andrew GenneryORCiD

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Background: Purine nucleoside phosphorylase (PNP) deficiency is a rare form of autosomal recessive combined primary immunodeficiency caused by a enzyme defect leading to the accumulation of inosine, 2'-deoxy-inosine (dIno), guanosine, and 2'-deoxy-guanosine (dGuo) in all cells, especially lymphocytes. Treatments are available and curative for PNP deficiency, but their efficacy depends on the early approach. PNP-combined immunodeficiency complies with the criteria for inclusion in a newborn screening program.Objective: This study evaluate whether mass spectrometry can identify metabolite abnormalities in dried blood spots (DBSs) from affected patients, with the final goal of individuating the disease at birth during routine newborn screening.Methods: DBS samples from 9 patients with genetically confirmed PNP-combined immunodeficiency, 10,000 DBS samples from healthy newborns, and 240 DBSs from healthy donors of different age ranges were examined. Inosine, dIno, guanosine, and dGuo were tested by using tandem mass spectrometry (TMS). T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) levels were evaluated by using quantitative RT-PCR only for the 2 patients (patients 8 and 9) whose neonatal DBSs were available.Results: Mean levels of guanosine, inosine, dGuo, and dIno were 4.4, 133.3, 3.6, and 3.8 mu mol/L, respectively, in affected patients. No indeterminate or false-positive results were found. In patient 8 TREC levels were borderline and KREC levels were abnormal; in patient 9 TRECs were undetectable, whereas KREC levels were normal.Conclusion: TMS is a valid method for diagnosis of PNP deficiency on DBSs of affected patients at a negligible cost. TMS identifies newborns with PNP deficiency, whereas TREC or KREC measurement alone can fail.


Publication metadata

Author(s): la Marca G, Canessa C, Giocaliere E, Romano F, Malvagia S, Funghini S, Moriondo M, Valleriani C, Lippi F, Ombrone D, Della Bona ML, Speckmann C, Borte S, Brodszki N, Gennery AR, Weinacht K, Celmeli F, Pagel J, de Martino M, Guerrini R, Wittkowski H, Santisteban I, Bali P, Ikinciogullari A, Hershfield M, Notarangelo LD, Resti M, Azzari C

Publication type: Article

Publication status: Published

Journal: Journal of Allergy and Clinical Immunology

Year: 2014

Volume: 134

Issue: 1

Pages: 155-159.e

Print publication date: 24/04/2014

ISSN (print): 0091-6749

ISSN (electronic): 1097-6825

Publisher: Mosby, Inc.

URL: http://dx.doi.org/10.1016/j.jaci.2014.01.040

DOI: 10.1016/j.jaci.2014.01.040


Altmetrics

Altmetrics provided by Altmetric


Share