title: TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease: A Systematic Review.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Pediatric Immunology and Infectious Diseases, University Medical Center Utrecht, Lundlaan 6, PO Box 85090, 3508 AB, Utrecht, The Netherlands.
authors.forename: Jet
authors.initials: J
authors.lastname: van der Spek
authors.forename: Rolf H H
authors.initials: RH
authors.lastname: Groenwold
authors.forename: Mirjam
authors.initials: M
authors.lastname: van der Burg
authors.forename: Joris M
authors.initials: JM
authors.lastname: van Montfrans
mesh_terms: D000465:Algorithms; D004270:DNA, Circular / Q000097:blood / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D015997:Neonatal Screening / Q000379:methods / Q000592:standards; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D004270:DNA, Circular; D011948:Receptors, Antigen, T-Cell