Newborn screening for Severe Combined Immunodeficiency - an ongoing successful story

Published: April 25, 2022

Severe combined immunodeficiency (SCID) is the most devastating inherited disease of the immune system with a fatal outcome early in life, unless diagnosis is performed promptly, and appropriate cautions and treatments are provided urgently. Early diagnosis can be achieved properly with identifying SCID cases during routine newborn screening (NBS) programs. Implementation of NBS programs for SCID became available using T cell receptor excision circle (TREC) based assays in Guthrie cards. Several open-questions still exist regarding the exact screening algorithm, appropriate TREC cutoff level, the validation process and the required follow up and management. Reporting long-term follow up of NBS for SCID enables clarifying these questions. Since October 2015, Israel does NBS for SCID on a national basis.

In The Journal of Allergy and Clinical Immunology: In Practice, Atar Lev and her colleagues reported their 5-year summary of NBS program for SCID in Israel. Immunological and genetic assessments, clinical analyses and outcome data from all infants screened positive were summarized. A total of 937,953 Guthrie cards were screened for SCID during 5 years, of them 142 newborns were referred to complete validation. Validation tests, including flow cytometry immune-phenotyping, TREC measurement in peripheral blood, and, in relevant cases, expression of TCRV? repertoire revealed specificity and sensitivity of 93.7% and 75.9%, respectively, in detecting true cases of SCID. The median of times elapsed from date of birth to the time of obtaining a second sample of Guthrie card and reporting final results were 9 and 13 days, respectively. Positive cases visited the national clinic for SCID at age of 20 days, and final diagnosis was reached at a median age of 27 days of birth. 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 non-SCID group of patients could be further sub classified into newborns with syndromes associated with T-cell impairment, idiopathic T cell lymphopenia, low immunity due to premature birth or secondary causes of lymphopenia.

Ethnicity and consanguineous marriage were found to be a risk for having an abnormal TREC result in the Israeli population. The most common genetic defects in this group were associated with autosomal recessive mutations in the DCLRE1C and IL7R? genes. No infant with SCID was missed during the study time making this program very successful. Twenty-two SCID patients underwent hematopoietic stem cell transplantation (HSCT) that resulted in a 91% survival rate. This national report adds to the growing evidence of the place of NBS for SCID is changing outcome and saving lives of affected infants.

This screening 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 of infants with SCID or other T cell lymphopenia and will enrich our understanding of immune development in health and disease.  

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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