TREC SCREENING

Characteristics of Disorders Characteristics of Test Well characterized pathogenesis Affects a significant number of infants Undetectable by routine examination Result in devastating consequences if not diagnosed/treated early Disease-altering treatment available High sensitivity and specificity Amenable for high- throughput screening Favorable cost-benefit analysis Low risk to infant Means of providing follow up Newborn Screening Chase. Curr. Opin. All. Imm. 2010, 10:521–5256

Generation of a unique T-cell receptor (TCR) clone begins by random selection and combination of TCR regions in germ line DNA The excised DNA sequences form a non- replicating episome TREC-positive cells are recent thymic emigrants T-Cell Receptor Excision Circles (TRECs)

Hazenberg. J. Mol. Med. 2001, 79:631–640 T-Cell Receptor Excision Circles (TRECs) TRECs can be detected in peripheral blood by quantitative PCR TREC levels correlate with numbers of naïve T- cells  Low TREC levels associated with SCID, diGeorge syndrome, congenital lymphopenia

* Hale. J. All. Clin. Immunol. 2010, 126:1073–4 T-Cell Receptor Excision Circles (TRECs) 2008: Wisconsin became first state to include TREC quantitation in the newborn screen 2009: The first infant with SCID identified in Massachusetts* 2010: TREC assay added to New York newborn screen

Chase. Curr. Opin. All. Imm. 2010, 10:521–5256

TREC Assay Pitfalls and Future Directions Reference ranges have not been established for neonates < 37 weeks corrected gestation Many abnormal TREC results have lead to diagnosis of undefined T-cell immunodeficiencies; without identifying underlying genetic defect optimal management remains uncertain Multi-plex quantitative PCR methods are being developed to screen for additional genetic diseases