Review
Newborn screening for SCID: where are we now? Expert Review of Clinical Immunology Downloaded from informahealthcare.com by Chinese University of Hong Kong on 02/15/15 For personal use only.
Expert Rev. Clin. Immunol. 10(12), 1649–1657 (2014)
Becky J Buelow1, John M Routes*1,2‡ and James W Verbsky1,2‡ 1 Department of Pediatrics, Medical College of Wisconsin, 9000 W Wisconsin Avenue, Suite 440, Milwaukee, WI, 53226, USA 2 Department of Microbiology and Molecular Genetics, Medical College of Wisconsin and the Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI, 53226, USA *Author for correspondence: Tel.: +1 414 266 6840 Fax: +1 414 266 6437 [email protected] ‡
Authors contributed equally
Newborn screening (NBS) for severe T-cell lymphopenia/severe combined immunodeficiency using the T-cell receptor excision circle assay continues to expand in the USA and worldwide. Here, we will review why severe combined immunodeficiency is an excellent case for NBS, the outcomes of the first 6 years of screening, and dilemmas surrounding screening and management of infants detected by NBS. We will also discuss the future of NBS for primary immunodeficiencies. KEYWORDS: newborn screening • severe combined immunodeficiency • T-cell lymphopenia • TREC
Historical background: why screen?
Population-based newborn screening (NBS) was implemented in 1963 when Guthrie and Susi proposed screening for phenylketonuria by tandem mass spectrometry using dried blood spots [1]. NBS has expanded to include 31 congenital disorders as recommended by the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children and an expert panel from the American College of Medical Genetics commissioned by the Health Resources and Services Administration [2,3]. Ethical controversies arose with the implementation of NBS, which resulted in the 1968 landmark paper by Wilson and Jungner, delineating 10 principles guiding NBS (BOX 1) [4]. These 10 principles continue to guide the development of NBS assays today. The continued discovery of disease-causing mutations is rapidly increasing with advances in high-throughput DNA sequencing of the human genome. Given these technologies, the ability to develop a test and implement it for population-based NBS of a life-threatening disease with favorable treatment options will continue to grow. Now, more than ever, it is important to carefully examine the costs and benefits of screening tests, and the NBS criteria by Wilson and Jungner can be a useful starting point in this regard. NBS for severe T-cell lymphopenia/severe combined immunodeficiency
Severe combined immunodeficiency (SCID) is a heterogeneous immunodeficiency characterized by severe T-cell lymphopenia (sTCL) (naı¨ve informahealthcare.com
10.1586/1744666X.2014.980816
T cells/CD45RA+
Newborn screening for SCID: where are we now? Expert Review of Clinical Immunology Downloaded from informahealthcare.com by Chinese University of Hong Kong on 02/15/15 For personal use only.
Expert Rev. Clin. Immunol. 10(12), 1649–1657 (2014)
Becky J Buelow1, John M Routes*1,2‡ and James W Verbsky1,2‡ 1 Department of Pediatrics, Medical College of Wisconsin, 9000 W Wisconsin Avenue, Suite 440, Milwaukee, WI, 53226, USA 2 Department of Microbiology and Molecular Genetics, Medical College of Wisconsin and the Children’s Research Institute, Medical College of Wisconsin, Milwaukee, WI, 53226, USA *Author for correspondence: Tel.: +1 414 266 6840 Fax: +1 414 266 6437 [email protected] ‡
Authors contributed equally
Newborn screening (NBS) for severe T-cell lymphopenia/severe combined immunodeficiency using the T-cell receptor excision circle assay continues to expand in the USA and worldwide. Here, we will review why severe combined immunodeficiency is an excellent case for NBS, the outcomes of the first 6 years of screening, and dilemmas surrounding screening and management of infants detected by NBS. We will also discuss the future of NBS for primary immunodeficiencies. KEYWORDS: newborn screening • severe combined immunodeficiency • T-cell lymphopenia • TREC
Historical background: why screen?
Population-based newborn screening (NBS) was implemented in 1963 when Guthrie and Susi proposed screening for phenylketonuria by tandem mass spectrometry using dried blood spots [1]. NBS has expanded to include 31 congenital disorders as recommended by the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children and an expert panel from the American College of Medical Genetics commissioned by the Health Resources and Services Administration [2,3]. Ethical controversies arose with the implementation of NBS, which resulted in the 1968 landmark paper by Wilson and Jungner, delineating 10 principles guiding NBS (BOX 1) [4]. These 10 principles continue to guide the development of NBS assays today. The continued discovery of disease-causing mutations is rapidly increasing with advances in high-throughput DNA sequencing of the human genome. Given these technologies, the ability to develop a test and implement it for population-based NBS of a life-threatening disease with favorable treatment options will continue to grow. Now, more than ever, it is important to carefully examine the costs and benefits of screening tests, and the NBS criteria by Wilson and Jungner can be a useful starting point in this regard. NBS for severe T-cell lymphopenia/severe combined immunodeficiency
Severe combined immunodeficiency (SCID) is a heterogeneous immunodeficiency characterized by severe T-cell lymphopenia (sTCL) (naı¨ve informahealthcare.com
10.1586/1744666X.2014.980816
T cells/CD45RA+
