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

Giancarlo La Marca, 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 FairbanksGiovanni Ragusa, Massimo Resti, Maurizio De Martino, Renzo Guerrini, Chiara Azzari

Research output: Contribution to journalArticle

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,

Original languageEnglish
Pages (from-to)1604-1610
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume131
Issue number6
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Adenosine deaminase
  • Adenosine deaminase-severe combined immunodeficiency
  • delayed-onset
  • genetics
  • inherited disorder
  • late-onset
  • newborn screening
  • severe combined immunodeficiency
  • T-cell receptor excision circle
  • tandem-mass-spectrometry

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    La Marca, G., Canessa, C., Giocaliere, E., Romano, F., Duse, M., Malvagia, S., Lippi, F., Funghini, S., Bianchi, L., Della Bona, M. L., Valleriani, C., Ombrone, D., Moriondo, M., Villanelli, F., Speckmann, C., Adams, S., Gaspar, B. H., Hershfield, M., Santisteban, I., ... Azzari, C. (2013). Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency. Journal of Allergy and Clinical Immunology, 131(6), 1604-1610. https://doi.org/10.1016/j.jaci.2012.08.054