Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency - PubMed (original) (raw)

Case Reports

. 2013 Jun;131(6):1604-10.

doi: 10.1016/j.jaci.2012.08.054. Epub 2012 Dec 30.

Clementina Canessa, Elisa Giocaliere, Francesca Romano, Marzia Duse, Sabrina Malvagia, Francesca Lippi, Silvia Funghini, Leila Bianchi, Maria Luisa Della Bona, Claudia Valleriani, Daniela Ombrone, Maria Moriondo, Fabio Villanelli, Carsten Speckmann, Stuart Adams, Bobby H Gaspar, Michael Hershfield, Ines Santisteban, Lynette Fairbanks, Giovanni Ragusa, Massimo Resti, Maurizio de Martino, Renzo Guerrini, Chiara Azzari

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Case Reports

Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency

Giancarlo la Marca et al. J Allergy Clin Immunol. 2013 Jun.

Abstract

Background: Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is caused by genetic variants that disrupt the function of ADA. In its early-onset form, it is rapidly fatal to infants. Delayed or late-onset ADA-SCID is characterized by insidious progressive immunodeficiency that leads to permanent organ damage or death. Quantification of T-cell receptor excision circles (TRECs) or tandem mass spectrometry (tandem-MS) analysis of dried blood spots (DBSs) collected at birth can identify newborns with early-onset ADA-SCID and are used in screening programs. However, it is not clear whether these analyses can identify newborns who will have delayed or late-onset ADA-SCID before symptoms appear.

Objective: We performed a retrospective study to evaluate whether tandem-MS and quantitative TREC analyses of DBSs could identify newborns who had delayed-onset ADA-SCID later in life.

Methods: We tested stored DBSs collected at birth from 3 patients with delayed-onset ADA-SCID using tandem-MS (PCT EP2010/070517) to evaluate levels of adenosine and 2'-deoxyadenosine and real-time PCR to quantify TREC levels. We also analyzed DBSs from 3 newborns with early-onset ADA-SCID and 2 healthy newborn carriers of ADA deficiency.

Results: The DBSs taken at birth from the 3 patients with delayed-onset ADA-SCID had adenosine levels of 10, 25, and 19 μmol/L (normal value, <1.5 μmol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 μmol/L (normal value, <0.07 μmol/L); the mean levels of adenosine and 2'-deoxyadenosine were respectively 12.0- and 27.6-fold higher than normal values. DBSs taken at birth from all 3 patients with delayed-onset ADA deficiency had normal TREC levels, but TRECs were undetectable in blood samples taken from the same patients at the time of diagnosis.

Conclusion: Tandem-MS but not TREC quantification identifies newborns with delayed- or late-onset ADA deficiency.

Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

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