Abstract
BackgroundNewborn 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.PurposeTo systematically review the diagnostic performance of published algorithms for TREC based NBS for SCID.MethodsPubMed, 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.ResultsThirteen 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).ConclusionsThe 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s10875-015-0152-6) contains supplementary material, which is available to authorized users.
Highlights
Severe combined immunodeficiency disease (SCID) is a group of inherited immunodeficiencies characterized by T cell lymphopenia (TCL)
This systematic review provides an overview of test characteristics, screening algorithm details, and test performances, and facilitates comparing the different screening programs which can be of help for states and countries that are in the process of preparing for implementation of T cell receptor excision circles (TRECs) based severe combined immunodeficiency disease (SCID) screening
This review reports the individual TREC values of typical SCID and other TCL patients detected by TREC-based Newborn screening (NBS), which is of importance for decision making on identification of other causes of TCL that can be identified by TREC based NBS
Summary
Severe combined immunodeficiency disease (SCID) is a group of inherited immunodeficiencies characterized by T cell lymphopenia (TCL). Survival of infants older than 3.5 months with active infection during transplant was only 50 %, indicating that early diagnosis of SCID improves outcome [4]. SCID can be detected early by quantifying T-cell receptor excision circles (TRECs) in Guthrie card dried blood spots (DBS) using a real time quantitative polymerase chain reaction (RT-qPCR) [5]. 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). 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
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