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

卷:131

Article

la Marca, Giancarlo^1,2  Canessa, Clementina^2,4  Giocaliere, Elisa^1,2  Romano, Francesca^2,4  Duse, Marzia⁵  Malvagia, Sabrina^1,2  Lippi, Francesca^2,4  Funghini, Silvia^1,2  Bianchi, Leila^2,4  Della Bona, Maria Luisa^1,2  Valleriani, Claudia^2,4  Ombrone, Daniela^1,2  Moriondo, Maria^2,4  Villanelli, Fabio^1,2  Speckmann, Carsten⁶  Adams, Stuart⁷  Gaspar, Bobby H.⁷  Hershfield, Michael⁸  Santisteban, Ines⁸  Fairbanks, Lynette⁷  Ragusa, Giovanni⁵  Resti, Massimo^2,4  de Martino, Maurizio^2,4  Guerrini, Renzo³  Azzari, Chiara^2,4 

[1] Univ Florence, Dept Pharmacol, I-50139 Florence, Italy

[2] Univ Florence, Anna Meyer Childrens Univ Hosp, I-50139 Florence, Italy

[3] Univ Florence, Clin Pediat Neurol, Dept Neurol, I-50139 Florence, Italy

[4] Univ Florence, Dept Women & Childrens Hlth, I-50139 Florence, Italy

[5] Univ Roma La Sapienza, Dept Pediat & Pediat Neuropsychiat, Rome, Italy

[6] Univ Freiburg, Ctr Chron Immundefizienz, Zentrum Kinderheilkunde & Jugendmed, Freiburg, Germany

[7] UCL Inst Child Hlth, Mol Immunol Unit, London, England

[8] Duke Univ, Med Ctr, Dept Med, Durham, NC 27706 USA

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;   

DOI  :  10.1016/j.jaci.2012.08.054

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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