History and current status of newborn screening for severe combined immunodeficiency

Semin Perinatol. 2015 Apr;39(3):194-205. doi: 10.1053/j.semperi.2015.03.004. Epub 2015 Apr 30.


The development of a T-cell receptor excision circle (TREC) assay utilizing dried blood spots in universal newborn screening has allowed the early detection of T-cell lymphopenia in newborns. Diagnosis of severe combined immunodeficiency (SCID) in affected infants in the neonatal period, while asymptomatic, permits early treatment and restoration of a functional immune system. SCID was the first immunodeficiency disease to be added to the Recommended Uniform Screening Panel of Core Conditions in the United States in 2010, and it is now implemented in 26 states in the U.S. This review covers the development of newborn screening for SCID, the biology of the TREC test, its current implementation in the U.S., new findings for SCID in the newborn screening era, and future directions.

Keywords: DiGeorge syndrome; T-cell lymphopenia; T-cell receptor excision circle (TREC); hematopoietic cell transplantation; primary immunodeficiency; severe combined immunodeficiency.

Publication types

  • Historical Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Dried Blood Spot Testing
  • Early Diagnosis
  • History, 20th Century
  • History, 21st Century
  • Humans
  • Infant, Newborn
  • Lymphopenia / diagnosis*
  • Lymphopenia / immunology
  • Neonatal Screening / history
  • Neonatal Screening / methods*
  • Neonatal Screening / trends
  • Severe Combined Immunodeficiency / diagnosis*
  • Severe Combined Immunodeficiency / immunology
  • T-Lymphocytes / immunology*
  • United States / epidemiology