George S Amatuni1,2, Robert J Currier1, Joseph A Church3, Tracey Bishop4, Elena Grimbacher5, Alan Anh-Chuong Nguyen6, Rajni Agarwal-Hashmi7, Constantino P Aznar4, Manish J Butte8, Morton J Cowan1, Morna J Dorsey1, Christopher C Dvorak1, Neena Kapoor3, Donald B Kohn8, M Louise Markert9, Theodore B Moore8, Stanley J Naides10, Stanley Sciortino4, Lisa Feuchtbaum4, Rasoul A Koupaei4, Jennifer M Puck11. 1. Department of Pediatrics, University of California, San Francisco and Benioff Children's Hospital, San Francisco, California. 2. Department of Cell Biology, Stem Cell Institute, Albert Einstein College of Medicine, Bronx, New York. 3. Department of Pediatrics, Keck School of Medicine, University of Southern California and Children's Hospital Los Angeles, Los Angeles, California. 4. Genetic Disease Screening Program, California Department of Public Health, Richmond, California. 5. School of Architecture and Urban Planning, University of Stuttgart, Stuttgart, Germany. 6. Broward Health Medical Center, Fort Lauderdale, Florida. 7. Department of Pediatrics, School of Medicine, Stanford University, Palo Alto, California. 8. Department of Pediatrics, University of California, Los Angeles and University of California, Los Angeles Mattel Children's Hospital, Los Angeles, California. 9. Department of Pediatrics, School of Medicine, Duke University, Durham, North Carolina; and. 10. Immunology Department, Quest Diagnostics Nichols Institute, San Juan Capistrano, California. 11. Department of Pediatrics, University of California, San Francisco and Benioff Children's Hospital, San Francisco, California; jennifer.puck@ucsf.edu.
Abstract
OBJECTIVES: Newborn screening for severe combined immunodeficiency (SCID) was instituted in California in 2010. In the ensuing 6.5 years, 3 252 156 infants in the state had DNA from dried blood spots assayed for T-cell receptor excision circles (TRECs). Abnormal TREC results were followed-up with liquid blood testing for T-cell abnormalities. We report the performance of the SCID screening program and the outcomes of infants who were identified. METHODS: Data that were reviewed and analyzed included demographics, nursery summaries, TREC and lymphocyte flow-cytometry values, and available follow-up, including clinical and genetic diagnoses, treatments, and outcomes. RESULTS: Infants with clinically significant T-cell lymphopenia (TCL) were successfully identified at a rate of 1 in 15 300 births. Of these, 50 cases of SCID, or 1 in 65 000 births (95% confidence interval 1 in 51 000-1 in 90 000) were found. Prompt treatment led to 94% survival. Infants with non-SCID TCL were also identified, diagnosed and managed, including 4 with complete DiGeorge syndrome who received thymus transplants. Although no cases of typical SCID are known to have been missed, 2 infants with delayed-onset leaky SCID had normal neonatal TREC screens but came to clinical attention at 7 and 23 months of age. CONCLUSIONS: Population-based TREC testing, although unable to detect immune defects in which T cells are present at birth, is effective for identifying SCID and clinically important TCL with high sensitivity and specificity. The experience in California supports the rapid, widespread adoption of SCID newborn screening.
OBJECTIVES: Newborn screening for severe combined immunodeficiency (SCID) was instituted in California in 2010. In the ensuing 6.5 years, 3 252 156 infants in the state had DNA from dried blood spots assayed for T-cell receptor excision circles (TRECs). Abnormal TREC results were followed-up with liquid blood testing for T-cell abnormalities. We report the performance of the SCID screening program and the outcomes of infants who were identified. METHODS: Data that were reviewed and analyzed included demographics, nursery summaries, TREC and lymphocyte flow-cytometry values, and available follow-up, including clinical and genetic diagnoses, treatments, and outcomes. RESULTS:Infants with clinically significant T-cell lymphopenia (TCL) were successfully identified at a rate of 1 in 15 300 births. Of these, 50 cases of SCID, or 1 in 65 000 births (95% confidence interval 1 in 51 000-1 in 90 000) were found. Prompt treatment led to 94% survival. Infants with non-SCIDTCL were also identified, diagnosed and managed, including 4 with complete DiGeorge syndrome who received thymus transplants. Although no cases of typical SCID are known to have been missed, 2 infants with delayed-onset leaky SCID had normal neonatal TREC screens but came to clinical attention at 7 and 23 months of age. CONCLUSIONS: Population-based TREC testing, although unable to detect immune defects in which T cells are present at birth, is effective for identifying SCID and clinically important TCL with high sensitivity and specificity. The experience in California supports the rapid, widespread adoption of SCID newborn screening.
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