Statewide newborn screening for severe T-cell lymphopenia.
BACKGROUND
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.


METHODS
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.


METHODS
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.


CONCLUSIONS
In a statewide screening program, use of the TREC assay performed on NBS cards was able to identify infants with T-cell lymphopenia.
Routes
John M
JM
Department of Pediatrics, Medical College of Wisconsin, and Children's Research Institute, Milwaukee, Wisconsin 53226-4874, USA. jroutes@mcw.edu
Grossman
William J
WJ
Verbsky
James
J
Laessig
Ronald H
RH
Hoffman
Gary L
GL
Brokopp
Charles D
CD
Baker
Mei W
MW
D006801:Humans; D016130:Immunophenotyping; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000175:diagnosis / Q000276:immunology; D008231:Lymphopenia / Q000175:diagnosis* / Q000209:etiology / Q000276:immunology; D015997:Neonatal Screening; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000097:blood / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis / Q000209:etiology / Q000276:immunology; D016176:T-Lymphocyte Subsets; D014922:Wisconsin
D011948:Receptors, Antigen, T-Cell