Statewide newborn screening for severe T-cell lymphopenia

JAMA. 2009 Dec 9;302(22):2465-70. doi: 10.1001/jama.2009.1806.


Context: A newborn blood screening (NBS) test that could identify infants with a profound deficiency of T cells may result in a reduction in mortality.

Objective: To determine if quantitating T-cell receptor excision circles (TRECs) using real-time quantitative polymerase chain reaction on DNA extracted from dried blood spots on NBS cards can detect infants with T-cell lymphopenia in a statewide program.

Design, setting, and participants: Between January 1 and December 31, 2008, the Wisconsin State Laboratory of Hygiene screened all infants born in Wisconsin for T-cell lymphopenia by quantitating the number of TRECs contained in a 3.2-mm punch (approximately 3 microL of whole blood) of the NBS card. Flow cytometry to enumerate the number of T cells was performed on full-term infants and preterm infants when they reached the equivalent of at least 37 weeks' gestation with TREC values of less than 25/microL. Infants with T-cell lymphopenia were evaluated by a clinical immunologist.

Main outcome measures: The number of infants with TREC values of less than 25/microL with T-cell lymphopenia confirmed by flow cytometry.

Results: Exactly 71,000 infants were screened by the TREC assay. Seventeen infants aged at least 37 weeks' gestation had at least 1 abnormal TREC assay (TREC values < 25/microL), 11 of whom had samples analyzed by flow cytometry to enumerate T cells. Eight infants demonstrated T-cell lymphopenia. The causes of the T-cell lymphopenia included DiGeorge syndrome (n = 2), idiopathic T-cell lymphopenia (n = 2), extravascular extravasation of lymphocytes (n = 3), and a Rac2 mutation (n = 1). The infant with the Rac2 mutation underwent successful cord blood transplantation.

Conclusion: In a statewide screening program, use of the TREC assay performed on NBS cards was able to identify infants with T-cell lymphopenia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Humans
  • Immunophenotyping
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / diagnosis
  • Infant, Premature, Diseases / immunology
  • Lymphopenia / diagnosis*
  • Lymphopenia / etiology
  • Lymphopenia / immunology
  • Neonatal Screening*
  • Polymerase Chain Reaction*
  • Receptors, Antigen, T-Cell* / blood
  • Receptors, Antigen, T-Cell* / genetics
  • Severe Combined Immunodeficiency / diagnosis
  • Severe Combined Immunodeficiency / etiology
  • Severe Combined Immunodeficiency / immunology
  • T-Lymphocyte Subsets
  • Wisconsin


  • Receptors, Antigen, T-Cell