TY - JOUR
T1 - Lessons Learned From Five Years of Newborn Screening for Severe Combined Immunodeficiency in Israel
AU - Lev, Atar
AU - Sharir, Idan
AU - Simon, Amos J.
AU - Levy, Shiran
AU - Lee, Yu Nee
AU - Frizinsky, Shirly
AU - Daas, Suha
AU - Saraf-Levy, Talia
AU - Broides, Arnon
AU - Nahum, Amit
AU - Hanna, Suhair
AU - Stepensky, Polina
AU - Toker, Ori
AU - Dalal, Ilan
AU - Etzioni, Amos
AU - Stein, Jerry
AU - Adam, Etai
AU - Hendel, Ayal
AU - Marcus, Nufar
AU - Almashanu, Shlomo
AU - Somech, Raz
N1 - Publisher Copyright: © 2022 American Academy of Allergy, Asthma & Immunology
PY - 2022/10/1
Y1 - 2022/10/1
N2 - Background: Implementation of newborn screening (NBS) programs for severe combined immunodeficiency (SCID) have advanced the diagnosis and management of affected infants and undoubtedly improved their outcomes. Reporting long-term follow-up of such programs is of great importance. Objective: We report a 5-year summary of the NBS program for SCID in Israel. Methods: Immunologic and genetic assessments, clinical analyses, and outcome data from all infants who screened positive were evaluated and summarized. Results: A total of 937,953 Guthrie cards were screened for SCID. A second Guthrie card was requested on 1,169 occasions (0.12%), which resulted in 142 referrals (0.015%) for further validation tests. Flow cytometry immune-phenotyping, T cell receptor excision circle measurement in peripheral blood, and expression of TCRVβ repertoire for the validation of positive cases revealed a specificity and sensitivity of 93.7% and 75.9%, respectively, in detecting true cases of SCID. Altogether, 32 SCID and 110 non-SCID newborns were diagnosed, making the incidence of SCID in Israel as high as 1:29,000 births. The most common genetic defects in this group were associated with mutations in DNA cross-link repair protein 1C and IL-7 receptor α (IL-7Rα) genes. No infant with SCID was missed during the study time. Twenty-two SCID patients underwent hematopoietic stem cell transplantation, which resulted in a 91% survival rate. Conclusions: Newborn screening for SCID should ultimately be applied globally, specifically to areas with high rates of consanguineous marriages. Accumulating data from follow-up studies on NBS for SCID will improve diagnosis and treatment and enrich our understanding of immune development in health and disease.
AB - Background: Implementation of newborn screening (NBS) programs for severe combined immunodeficiency (SCID) have advanced the diagnosis and management of affected infants and undoubtedly improved their outcomes. Reporting long-term follow-up of such programs is of great importance. Objective: We report a 5-year summary of the NBS program for SCID in Israel. Methods: Immunologic and genetic assessments, clinical analyses, and outcome data from all infants who screened positive were evaluated and summarized. Results: A total of 937,953 Guthrie cards were screened for SCID. A second Guthrie card was requested on 1,169 occasions (0.12%), which resulted in 142 referrals (0.015%) for further validation tests. Flow cytometry immune-phenotyping, T cell receptor excision circle measurement in peripheral blood, and expression of TCRVβ repertoire for the validation of positive cases revealed a specificity and sensitivity of 93.7% and 75.9%, respectively, in detecting true cases of SCID. Altogether, 32 SCID and 110 non-SCID newborns were diagnosed, making the incidence of SCID in Israel as high as 1:29,000 births. The most common genetic defects in this group were associated with mutations in DNA cross-link repair protein 1C and IL-7 receptor α (IL-7Rα) genes. No infant with SCID was missed during the study time. Twenty-two SCID patients underwent hematopoietic stem cell transplantation, which resulted in a 91% survival rate. Conclusions: Newborn screening for SCID should ultimately be applied globally, specifically to areas with high rates of consanguineous marriages. Accumulating data from follow-up studies on NBS for SCID will improve diagnosis and treatment and enrich our understanding of immune development in health and disease.
KW - Dry blood spots
KW - Hematopoietic stem cell transplantation
KW - Newborn screening
KW - Primary immunodeficiency
KW - SCID
KW - Severe combined immunodeficiency
KW - T cell lymphopenia
UR - http://www.scopus.com/inward/record.url?scp=85131835528&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jaip.2022.04.013
DO - https://doi.org/10.1016/j.jaip.2022.04.013
M3 - Article
C2 - 35487367
SN - 2213-2198
VL - 10
SP - 2722-2731.e9
JO - Journal of Allergy and Clinical Immunology: In Practice
JF - Journal of Allergy and Clinical Immunology: In Practice
IS - 10
ER -
