Background: Implementation of newborn screening (NBS) programs for severe combined immunodeficiency (SCID) have advanced diagnosis and management of affected infants and undoubtedly improved their outcomes. Reporting long-term follow-up of such programs is of great importance.
Objective: Here we report a five-year summary of the NBS program for SCID in Israel.
Methods: Immunological and genetic assessments, clinical analyses and outcome data from all infants 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 1169 occasions (0.12%) that resulted in 142 referrals (0.015%) for further validation tests. Flow cytometry immune-phenotyping, TREC measurement in peripheral blood, and expression of TCRVβ repertoire for validation of positive cases revealed 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 DCLRE1C and IL7R genes. No infant with SCID was missed during the study time. Twenty-two SCID patients underwent hematopoietic stem cell transplantation (HSCT) that resulted in a 91% survival rate.
Conclusions: NBS for SCID should be ultimately applied globally, specifically to areas with high rates of consanguineous marriages. Accumulating data from follow-up studies on NBS for SCID will enable improving diagnosis and treatment and will enrich our understanding of immune development in health and disease.
Keywords: Dry blood spots; Hematopoietic stem cell transplantation; Primary immunodeficiency; SCID; Severe combined immunodeficiency; T cell lymphopenia; newborn screening.
Copyright © 2022. Published by Elsevier Inc.