Statewide Newborn Screening for Severe T-Cell Lymphopenia
- John M. Routes, MD;
- William J. Grossman, MD, PhD;
- James Verbsky, MD, PhD;
- Ronald H. Laessig, PhD†;
- Gary L. Hoffman, BS;
- Charles D. Brokopp, DrPH;
- Mei W. Baker, MD
- Author Affiliations: Department of Pediatrics, Medical College of Wisconsin, and Children's Research Institute, Milwaukee, Wisconsin (Drs Routes, Grossman, and Verbsky); Wisconsin State Laboratory of Hygiene (Drs Laessig, Brokopp, and Baker, and Mr Hoffman) and Departments of Population Health Sciences (Drs Laessig and Brokopp) and Pediatrics (Dr Baker), University of Wisconsin School of Medicine and Public Health, Madison. Dr Grossman is now with Clinical Oncology, Merck, North Wales, Pennsylvania.†Deceased.
Abstract
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 μL 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/μL. 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/μL 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/μL), 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.
