期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 131, 期 6, 页码 1604-1610出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2012.08.054
关键词
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
资金
- University of Florence
- Anna Meyer Children's University Hospital
- Tuscany (Italy) region
- Sigma-Tau Pharmaceuticals
- Great Ormond Street Hospital Childrens Charity [V1242] Funding Source: researchfish
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.
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