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Population-based newborn screening for severe combined immunodeficiency: Steps toward implementation

  • Jennifer M. Puck
    Correspondence
    Reprint requests: Jennifer M. Puck, MD, Department of Pediatrics, Box 0519, University of California, San Francisco, 513 Parnassus Avenue, HSE 301A, San Francisco, CA 94143-0519.
    Affiliations
    Department of Pediatrics, University of California, San Francisco, Calif
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  • Affiliations
    The SCID Newborn Screening Working Group met in San Francisco, May 14-15, 2007. The group includes John C. Baker (Kaiser Permanente, Oakland Medical Center, Oakland, Calif); Mei W. Baker (University of Wisconsin, Madison); Marcia Boyle (Immune Deficiency Foundation, Towson, Md); Amy Brower (Third Wave Technologies, Madison, Wis); Rebecca H. Buckley (Duke University Medical Center, Durham, NC); Fabio Candotti (National Human Genome Research Institute, National Institutes of Health, Bethesda, Md); Anne Marie Comeau (University of Massachusetts Medical School, Jamaica Plain); Morton Cowan (University of California, San Francisco); Joie Davis (National Human Genome Research Institute, National Institutes of Health, Bethesda, Md); Elaine Eastman (Kaiser Permanente, Oakland Medical Center, Oakland, Calif); Gilian Engelson (National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md); Diana Gonzalez-Espinosa (University of California, San Francisco); Nancy S. Green (Columbia University Medical Center, New York, NY); Howard Grodman (Tufts New England Medical Center, Boston, Mass); William Grossman (Medical College of Wisconsin, Milwaukee); R. Rodney Howell (National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Md); Naynesh R. Kamani (Children's National Medical Center, Washington, DC); Martin Kharrazi (California Department of Public Health, Richmond); Alan P. Knutsen (St Louis University School of Medicine, St Louis, Mo); Ronald H. Laessig (University of Wisconsin/State Lab of Hygiene, Madison); Tonya Lebet (University of California, San Francisco); Howard M. Lederman, Johns Hopkins School of Medicine, Baltimore, Md); David Lewis (Stanford University Medical Center, Palo Alto, Calif); Fred Lorey (California Department of Public Health, Richmond); Fizza Gulamali-Majid (Maryland State Department of Health and Mental Hygiene, Baltimore); Elaine Mansfield (Affymetrix, Santa Clara, Calif); Louis Matis (Immune Tolerance Institute, Inc, Southport, Ct); Sean McGhee (University of California Los Angeles Center for Health Sciences, Los Angeles); Fred Modell (Jeffrey Modell Foundation, New York, NY); Vicki Modell (Jeffrey Modell Foundation, New York, NY); Luigi Notarangelo (Harvard Medical School, Boston, Mass); Richard S. Olney (Centers for Disease Control and Prevention, Atlanta, Ga); Joseph J. Orsini (Wadsworth Center, New York State Department of Health, Albany); Sung-Yun Pai (Harvard Medical School and Childrens Hospital, Boston, Mass); Susan R. Panny (Maryland State Department of Health and Mental Hygiene, Baltimore); Kenneth Pass (Wadsworth Center, New York State Department of Health, Albany, NY); Susan Prockop (Memorial Hospital/Sloan-Kettering, New York, NY); Jennifer M. Puck (University of California, San Francisco); Michele A. Lloyd-Puryear (Maternal and Child Health Bureau, Health Resources Services Administration, Department of Health and Human Services, Rockville, Md); John M. Routes (Medical College of Wisconsin, Milwaukee); John E. Sherwin (California Department of Public Health, Richmond); Bradford L. Therrell, Jr (National Newborn Screening and Genetics Resource Center, University of Texas Health Science Center at San Antonio); Troy Torgerson (University of Washington and Seattle Childrens Hospital, Seattle); Robert F. Vogt, Jr (Centers for Disease Control and Prevention, Atlanta, Ga); Diane Wara (University of California, San Francisco); and Kenneth Weinberg (Stanford University Medical Center, Palo Alto, Calif)
      Severe combined immune deficiency (SCID) has been identified as a disorder of high priority for population-based newborn screening. Most affected infants are not brought to medical attention until they develop serious infectious complications, and SCID is fatal if untreated. Effective treatment with allogeneic hematopoietic stem cell transplantation is widely established. The best outcome for SCID, as with many other conditions for which newborn screening is now done, is achieved if hematopoietic stem cell transplantation is performed in the first months of life, ideally before clinical presentation with infections and failure to thrive. A meeting in San Francisco in May 2007 brought together experts from newborn screening programs; the pediatric immunology community; pediatric transplant centers; and federal, state, and nongovernmental agencies to consider obstacles to and implications of developing newborn screening for SCID. Development of an appropriate low-cost, high-throughput screening algorithm has been a challenge, although absence of T-cell receptor gene excision circles is a sensitive marker of profound T lymphocytopenia and currently is the most developed screening method. A consensus was reached on several points: SCID newborn screening should be pursued with pilot studies in key locales, test methodologies need to be optimized, screening programs must be integrated with plans for definitive diagnosis and management, centralized specimen banks and registries are required to foster test validation and track outcomes that will guide future treatment, and SCID newborn screening will lead to important knowledge about human immune disorders as well as better care of patients.

      Key words

      Abbreviations used:

      DBS (Dried blood spot), HSCT (Hematopoietic stem cell transplantation), NK (Natural killer), SCID (Severe combined immunodeficiency), TREC (T-cell receptor gene excision circle)
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