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Journal of Clinical Immunology
Published in: Journal of Clinical Immunology 4/2015

Open Access 01-05-2015 | Original Research

TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease: A Systematic Review

Authors: Jet van der Spek, Rolf H. H. Groenwold, Mirjam van der Burg, Joris M. van Montfrans

Published in: Journal of Clinical Immunology | Issue 4/2015

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Abstract

Background

Newborn screening (NBS) by quantifying T cell receptor excision circles (TRECs) in neonatal dried blood spots (DBS) enables early diagnosis of severe combined immunodeficiency disease (SCID). In recent years, different screening algorithms for TREC based SCID screening were reported.

Purpose

To systematically review the diagnostic performance of published algorithms for TREC based NBS for SCID.

Methods

PubMed, EMBASE and the Cochrane Library were systematically searched for case series and prospective cohort studies describing TREC based NBS for SCID. We extracted TREC content and cut-off values, number of retests, repeat DBS and referrals, and type and number of typical SCID and other T cell lymphopenia (TCL) cases. We calculated positive predictive value (PPV), test sensitivity and SCID incidence.

Results

Thirteen studies were included, re-confirming 89 known SCID cases in case series and reporting 53 new SCID cases in 3.15 million newborns. In case series, the sensitivity for typical SCID was 100 %. In the prospective cohort studies, SCID incidence was ~1.7:100,000, re-test rate was 0.20–3.26 %, repeat DBS rate 0.0–0.41 % and referral rate 0.01–1.35 %. PPV within the five largest cohorts was 0.8–11.2 % for SCID and 18.3–81.0 % for TCL. Individual TREC contents in all SCID patients was <25 TRECs/μl (except in those evaluated with the New York State assay).

Conclusions

The sensitivity of TREC based NBS for typical SCID was 100 %. The TREC cut-off score determines the percentage of non-SCID TCL cases detected in newborn screening for TCL. Adapting the screening algorithm for pre-term/ill infants reduces the amount of false positive test results.
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Metadata
Title
TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease: A Systematic Review
Authors
Jet van der Spek
Rolf H. H. Groenwold
Mirjam van der Burg
Joris M. van Montfrans
Publication date
01-05-2015
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 4/2015
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-015-0152-6

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