Lessons Learned From Five Years of Newborn Screening for Severe Combined Immunodeficiency in Israel

Atar Lev, Idan Sharir, Amos J. Simon, Shiran Levy, Yu Nee Lee, Shirly Frizinsky, Suha Daas, Talia Saraf-Levy, Arnon Broides, Amit Nahum, Suhair Hanna, Polina Stepensky, Ori Toker, Ilan Dalal, Amos Etzioni, Jerry Stein, Etai Adam, Ayal Hendel, Nufar Marcus, Shlomo AlmashanuRaz Somech

    Research output: Contribution to journalArticlepeer-review

    9 Scopus citations


    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.

    Original languageEnglish
    Pages (from-to)2722-2731.e9
    JournalJournal of Allergy and Clinical Immunology: In Practice
    Issue number10
    StatePublished - 1 Oct 2022


    • Dry blood spots
    • Hematopoietic stem cell transplantation
    • Newborn screening
    • Primary immunodeficiency
    • SCID
    • Severe combined immunodeficiency
    • T cell lymphopenia

    ASJC Scopus subject areas

    • Immunology and Allergy


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