. 2014 Aug 20;312(7):729-38.

doi: 10.1001/jama.2014.9132.

Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States

Antonia Kwan¹, Roshini S Abraham², Robert Currier³, Amy Brower⁴, Karen Andruszewski⁵, Jordan K Abbott⁶, Mei Baker⁷, Mark Ballow⁸, Louis E Bartoshesky⁹, Francisco A Bonilla¹⁰, Charles Brokopp¹¹, Edward Brooks¹², Michele Caggana¹³, Jocelyn Celestin¹⁴, Joseph A Church¹⁵, Anne Marie Comeau¹⁶, James A Connelly¹⁷, Morton J Cowan¹, Charlotte Cunningham-Rundles¹⁸, Trivikram Dasu¹⁹, Nina Dave²⁰, Maria T De La Morena²¹, Ulrich Duffner²², Chin-To Fong²³, Lisa Forbes²⁴, Debra Freedenberg²⁵, Erwin W Gelfand⁶, Jaime E Hale²⁶, I Celine Hanson²⁴, Beverly N Hay²⁷, Diana Hu²⁸, Anthony Infante¹², Daisy Johnson²⁵, Neena Kapoor¹⁵, Denise M Kay¹³, Donald B Kohn²⁹, Rachel Lee²⁵, Heather Lehman⁸, Zhili Lin³⁰, Fred Lorey³, Aly Abdel-Mageed²², Adrienne Manning³¹, Sean McGhee³², Theodore B Moore²⁹, Stanley J Naides³³, Luigi D Notarangelo¹⁰, Jordan S Orange²⁴, Sung-Yun Pai¹⁰, Matthew Porteus³², Ray Rodriguez²⁰, Neil Romberg³⁴, John Routes³⁵, Mary Ruehle³⁶, Arye Rubenstein³⁷, Carlos A Saavedra-Matiz¹³, Ginger Scott²⁵, Patricia M Scott³⁸, Elizabeth Secord³⁶, Christine Seroogy³⁹, William T Shearer²⁴, Subhadra Siegel⁴⁰, Stacy K Silvers⁴¹, E Richard Stiehm²⁹, Robert W Sugerman⁴¹, John L Sullivan²⁷, Susan Tanksley²⁵, Millard L Tierce 4th³⁶, James Verbsky³⁵, Beth Vogel¹³, Rosalyn Walker²⁰, Kelly Walkovich¹⁷, Jolan E Walter⁴², Richard L Wasserman⁴¹, Michael S Watson⁴, Geoffrey A Weinberg²³, Leonard B Weiner⁴³, Heather Wood⁵, Anne B Yates²⁰, Jennifer M Puck¹, Vincent R Bonagura

Affiliations

¹ Department of Pediatrics, University of California, San Francisco, San Francisco2UCSF Benioff Children's Hospital, San Francisco, California.
² Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
³ Genetic Disease Screening Program, California Department of Public Health, Richmond.
⁴ Newborn Screening Translational Research Network, American College of Medical Genetics and Genomics, Bethesda, Maryland.
⁵ Michigan Department of Community Health, Lansing.
⁶ Division of Allergy and Immunology, Department of Pediatrics, National Jewish Health, Denver, Colorado.
⁷ Newborn Screening Laboratory, Wisconsin State Laboratory of Hygiene, Madison9Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison.
⁸ Women and Children's Hospital of Buffalo, Buffalo, New York.
⁹ Department of Pediatrics, Christiana Care Health System, Wilmington, Delaware.
¹⁰ Department of Medicine, Boston Children's Hospital, Boston, Massachusetts13Harvard Medical School, Boston, Massachusetts.
¹¹ Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
¹² Department of Pediatrics, University of Texas Health Science Center at San Antonio.
¹³ Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany.
¹⁴ Division of Allergy and Immunology, Albany Medical College, Albany, New York.
¹⁵ Department of Pediatrics, University of Southern California, Los Angeles19Children's Hospital Los Angeles, Los Angeles, California.
¹⁶ New England Newborn Screening Program, University of Massachusetts Medical School, Jamaica Plain31 Department of Pediatrics, University of Massachusetts Medical School, Worcester.
¹⁷ University of Michigan C. S. Mott Children's Hospital, Ann Arbor.
¹⁸ Mount Sinai Medical Center, New York, New York.
¹⁹ Clinical Immunodiagnostic and Research Laboratory, Medical College of Wisconsin, Milwaukee.
²⁰ Department of Pediatrics, University of Mississippi Medical Center, Jackson.
²¹ Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas.
²² Division of Blood and Bone Marrow Transplantation, Helen DeVos Children's Hospital, Grand Rapids, Michigan.
²³ University of Rochester School of Medicine and Dentistry, Rochester, New York.
²⁴ Department of Pediatrics, Baylor College of Medicine, Houston, Texas29Texas Children's Hospital, Houston.
²⁵ Texas Department of State Health Services, Austin.
²⁶ New England Newborn Screening Program, University of Massachusetts Medical School, Jamaica Plain.
²⁷ Department of Pediatrics, University of Massachusetts Medical School, Worcester.
²⁸ Tuba City Regional Health Care, Tuba City, Arizona.
²⁹ Department of Pediatrics, University of California, Los Angeles, Los Angeles.
³⁰ PerkinElmer Genetics, Bridgeville, Pennsylvania.
³¹ Connecticut Department of Public Health Laboratory, Rocky Hill.
³² Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California37Lucille Packard Children's Hospital, Palo Alto, California.
³³ Immunology Department, Quest Diagnostics Nichols Institute, San Juan Capistrano, California.
³⁴ Division of Allergy and Clinical Immunology, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut.
³⁵ Department of Pediatrics, Children's Research Institute, Medical College of Wisconsin, Milwaukee.
³⁶ Children's Hospital of Michigan, Detroit.
³⁷ Division of Allergy and Immunology, Montefiore Medical Park, Bronx, New York.
³⁸ Newborn Screening Program, Delaware Public Health Laboratory, Smyrna.
³⁹ Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison.
⁴⁰ New York Medical College, Westchester Medical Center, Valhalla, New York.
⁴¹ Medical City Children's Hospital, Dallas, Texas.
⁴² Department of Pediatrics, Massachusetts General Hospital, Boston48Harvard Medical School, Boston, Massachusetts.
⁴³ Department of Pediatrics, State University of New York Upstate Medical University, Syracuse.

PMID: 25138334
PMCID: PMC4492158
DOI: 10.1001/jama.2014.9132

Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States

Antonia Kwan et al. JAMA. 2014.

. 2014 Aug 20;312(7):729-38.

doi: 10.1001/jama.2014.9132.

Authors

Affiliations

¹ Department of Pediatrics, University of California, San Francisco, San Francisco2UCSF Benioff Children's Hospital, San Francisco, California.
² Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
³ Genetic Disease Screening Program, California Department of Public Health, Richmond.
⁴ Newborn Screening Translational Research Network, American College of Medical Genetics and Genomics, Bethesda, Maryland.
⁵ Michigan Department of Community Health, Lansing.
⁶ Division of Allergy and Immunology, Department of Pediatrics, National Jewish Health, Denver, Colorado.
⁷ Newborn Screening Laboratory, Wisconsin State Laboratory of Hygiene, Madison9Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison.
⁸ Women and Children's Hospital of Buffalo, Buffalo, New York.
⁹ Department of Pediatrics, Christiana Care Health System, Wilmington, Delaware.
¹⁰ Department of Medicine, Boston Children's Hospital, Boston, Massachusetts13Harvard Medical School, Boston, Massachusetts.
¹¹ Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison.
¹² Department of Pediatrics, University of Texas Health Science Center at San Antonio.
¹³ Newborn Screening Program, Wadsworth Center, New York State Department of Health, Albany.
¹⁴ Division of Allergy and Immunology, Albany Medical College, Albany, New York.
¹⁵ Department of Pediatrics, University of Southern California, Los Angeles19Children's Hospital Los Angeles, Los Angeles, California.
¹⁶ New England Newborn Screening Program, University of Massachusetts Medical School, Jamaica Plain31 Department of Pediatrics, University of Massachusetts Medical School, Worcester.
¹⁷ University of Michigan C. S. Mott Children's Hospital, Ann Arbor.
¹⁸ Mount Sinai Medical Center, New York, New York.
¹⁹ Clinical Immunodiagnostic and Research Laboratory, Medical College of Wisconsin, Milwaukee.
²⁰ Department of Pediatrics, University of Mississippi Medical Center, Jackson.
²¹ Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas.
²² Division of Blood and Bone Marrow Transplantation, Helen DeVos Children's Hospital, Grand Rapids, Michigan.
²³ University of Rochester School of Medicine and Dentistry, Rochester, New York.
²⁴ Department of Pediatrics, Baylor College of Medicine, Houston, Texas29Texas Children's Hospital, Houston.
²⁵ Texas Department of State Health Services, Austin.
²⁶ New England Newborn Screening Program, University of Massachusetts Medical School, Jamaica Plain.
²⁷ Department of Pediatrics, University of Massachusetts Medical School, Worcester.
²⁸ Tuba City Regional Health Care, Tuba City, Arizona.
²⁹ Department of Pediatrics, University of California, Los Angeles, Los Angeles.
³⁰ PerkinElmer Genetics, Bridgeville, Pennsylvania.
³¹ Connecticut Department of Public Health Laboratory, Rocky Hill.
³² Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California37Lucille Packard Children's Hospital, Palo Alto, California.
³³ Immunology Department, Quest Diagnostics Nichols Institute, San Juan Capistrano, California.
³⁴ Division of Allergy and Clinical Immunology, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut.
³⁵ Department of Pediatrics, Children's Research Institute, Medical College of Wisconsin, Milwaukee.
³⁶ Children's Hospital of Michigan, Detroit.
³⁷ Division of Allergy and Immunology, Montefiore Medical Park, Bronx, New York.
³⁸ Newborn Screening Program, Delaware Public Health Laboratory, Smyrna.
³⁹ Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison.
⁴⁰ New York Medical College, Westchester Medical Center, Valhalla, New York.
⁴¹ Medical City Children's Hospital, Dallas, Texas.
⁴² Department of Pediatrics, Massachusetts General Hospital, Boston48Harvard Medical School, Boston, Massachusetts.
⁴³ Department of Pediatrics, State University of New York Upstate Medical University, Syracuse.

PMID: 25138334
PMCID: PMC4492158
DOI: 10.1001/jama.2014.9132

Erratum in

JAMA. 2014 Nov 26;312(20):2169. Bonagura, Vincent R [Added]

Abstract

Importance: Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100,000 births.

Objectives: To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments.

Design: Epidemiological and retrospective observational study.

Setting: Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3,030,083 newborns screened with a TREC test.

Main outcomes and measures: Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked.

Results: Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58,000 infants (95% CI, 1/46,000-1/80,000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87% (45/52), 92% (45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia.

Conclusions and relevance: Newborn screening in 11 programs in the United States identified SCID in 1 in 58,000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Bonagura reported receiving grants from the Jeffrey Modell Foundation, Baxter Pharmaceuticals, and New York State; serving on a committee for CSL-Behring; and serving on an advisory board for Baxter Pharmaceuticals. No other disclosures were reported.

Comment in

Newborn screening for severe combined immunodeficiency: progress and challenges.
Holtzman NA. Holtzman NA. JAMA. 2014 Aug 20;312(7):701-2. doi: 10.1001/jama.2014.9133. JAMA. 2014. PMID: 25138331 No abstract available.

References

1. Al-Herz W, Bousfiha A, Casanova JL, et al. Primary immunodeficiency diseases: an update on the classification from the International Union of Immunological Societies expert committee for primary immunodeficiency. Front Immunol. 2014;5:162. - PMC - PubMed
1. Buckley RH. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Annu Rev Immunol. 2004;22:625–655. - PubMed
1. Myers LA, Patel DD, Puck JM, Buckley RH. Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival. Blood. 2002;99(3):872–878. - PubMed
1. Brown L, Xu-Bayford J, Allwood Z, et al. Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood. 2011;117(11):3243–3246. - PubMed
1. Dvorak CC, Cowan MJ, Logan BR, et al. The natural history of children with severe combined immunodeficiency: baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901. J Clin Immunol. 2013;33(7):1156–1164. - PMC - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States

Affiliations

Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Comment in

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical