Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency - 30/05/13
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.
Le texte complet de cet article est disponible en PDF.Key words : Adenosine deaminase, severe combined immunodeficiency, newborn screening, tandem-mass-spectrometry, late-onset, delayed-onset, Adenosine deaminase–severe combined immunodeficiency, T-cell receptor excision circle, genetics, inherited disorder
Abbreviations used : ADA, dAXP, DBS, SCID, Tandem-MS, TREC
Plan
| Supported in part by a donation from Famiglia Cassigoli (C.A.) and a grant from the University of Florence (C.A. and G.l.M.), the Anna Meyer Children's University Hospital (M.R.), and the Tuscany (Italy) region (C.A., G.l.M., and M.R.). Sigma-Tau Pharmaceuticals provided grant support to M.H. and I.S. |
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| Disclosure of potential conflict of interest: B. H. Gaspar has consultant arrangements with Enzon. I. Santisteban and M. Hershfield have received grants from Sigma-Tau Pharmaceuticals. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 131 - N° 6
P. 1604-1610 - juin 2013 Retour au numéro
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