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 mu mol/L (normal value, <1.5 mu mol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 mu mol/L (normal value, <0.07 mu mol/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.
Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency / G., La Marca; Clementina, Canessa; Elisa, Giocaliere; Francesca, Romano; Duse, Marzia; 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; Ragusa, Giovanni; Massimo, Resti; M., De Martino; Renzo, Guerrini; Chiara, Azzari. - In: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY. - ISSN 0091-6749. - STAMPA. - 131:6(2013), pp. 1604-1610. [10.1016/j.jaci.2012.08.054]
Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency
DUSE, MARZIA;RAGUSA, GIOVANNI;
2013
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 mu mol/L (normal value, <1.5 mu mol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 mu mol/L (normal value, <0.07 mu mol/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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
