Statewide Newborn Screening for Severe T-Cell Lymphopenia

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 mu L 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/mu L. 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/mu L 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/mu L), 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. JAMA. 2009; 302(22): 2465-2470