Diagnosis of immunodeficiency caused by a purine nucleoside phosphorylase defect by using tandem mass spectrometry on dried blood spots
Standard
Diagnosis of immunodeficiency caused by a purine nucleoside phosphorylase defect by using tandem mass spectrometry on dried blood spots. / la Marca, Giancarlo; Canessa, Clementina; Giocaliere, Elisa; Romano, Francesca; Malvagia, Sabrina; Funghini, Silvia; Moriondo, Maria; Valleriani, Claudia; Lippi, Francesca; Ombrone, Daniela; Della Bona, Maria Luisa; Speckmann, Carsten; Borte, Stephan; Brodszki, Nicholas; Gennery, Andrew R; Weinacht, Katja; Celmeli, Fatih; Pagel, Julia; de Martino, Maurizio; Guerrini, Renzo; Wittkowski, Helmut; Santisteban, Ines; Bali, Pawan; Ikinciogullari, Aydan; Hershfield, Michael; Notarangelo, Luigi D; Resti, Massimo; Azzari, Chiara.
in: J ALLERGY CLIN IMMUN, Jahrgang 134, Nr. 1, 07.2014, S. 155-9.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Diagnosis of immunodeficiency caused by a purine nucleoside phosphorylase defect by using tandem mass spectrometry on dried blood spots
AU - la Marca, Giancarlo
AU - Canessa, Clementina
AU - Giocaliere, Elisa
AU - Romano, Francesca
AU - Malvagia, Sabrina
AU - Funghini, Silvia
AU - Moriondo, Maria
AU - Valleriani, Claudia
AU - Lippi, Francesca
AU - Ombrone, Daniela
AU - Della Bona, Maria Luisa
AU - Speckmann, Carsten
AU - Borte, Stephan
AU - Brodszki, Nicholas
AU - Gennery, Andrew R
AU - Weinacht, Katja
AU - Celmeli, Fatih
AU - Pagel, Julia
AU - de Martino, Maurizio
AU - Guerrini, Renzo
AU - Wittkowski, Helmut
AU - Santisteban, Ines
AU - Bali, Pawan
AU - Ikinciogullari, Aydan
AU - Hershfield, Michael
AU - Notarangelo, Luigi D
AU - Resti, Massimo
AU - Azzari, Chiara
N1 - Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
PY - 2014/7
Y1 - 2014/7
N2 - 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 μmol/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.
AB - 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 μmol/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.
KW - Adolescent
KW - Child, Preschool
KW - DNA Repair
KW - Deoxyguanosine/analysis
KW - Dried Blood Spot Testing
KW - Female
KW - Guanosine/analysis
KW - Humans
KW - Immunologic Deficiency Syndromes/diagnosis
KW - Infant
KW - Infant, Newborn
KW - Inosine/analogs & derivatives
KW - Lymphocytes/pathology
KW - Male
KW - Mutation
KW - Neonatal Screening
KW - Primary Immunodeficiency Diseases
KW - Purine-Nucleoside Phosphorylase/deficiency
KW - Purine-Pyrimidine Metabolism, Inborn Errors/diagnosis
KW - Tandem Mass Spectrometry
U2 - 10.1016/j.jaci.2014.01.040
DO - 10.1016/j.jaci.2014.01.040
M3 - SCORING: Journal article
C2 - 24767876
VL - 134
SP - 155
EP - 159
JO - J ALLERGY CLIN IMMUN
JF - J ALLERGY CLIN IMMUN
SN - 0091-6749
IS - 1
ER -