Newborn Screening for Severe Combined Immunodeficiency in Israel

Abstract

Newborn screening (NBS) programs for severe combined immunodeficiency (SCID), the most severe type of primary immunodeficiency, are being implemented in more and more countries with every passing year. Since October 2015, SCID screening via T cell receptor excision circle (TREC) quantification in dried blood spots (DBS) has been part of the Israeli NBS program. As an NBS program in its infancy, SCID screening is still evolving, making gathering input from the various programs crucial for compiling an ideal screening algorithm. The relatively high rate of consanguineous marriages in Israel, especially among non-Jews, correlates with an increased incidence of SCID. The Israeli algorithm uses a commercial kit and consists of a two-Guthrie card confirmation system prior to referral to a national immunology center. Preliminary data from the first year and a half of SCID screening in Israel has identified a surprisingly high prevalence of DNA cross-link repair protein 1c (DCLRE1C; ARTEMIS) mutations as the cause of SCID in Israel. The clinically unbiased nature of SCID screening helps unearth mild/leaky SCID phenotypes, resulting in a better understanding of true SCID prevalence and etiology.

First Year of Israeli Newborn Screening for Severe Combined Immunodeficiency—Clinical Achievements and Insights

“…T cell receptor excision circle cutoff for retesting was initially set at 36 copies per blood spot and was gradually lowered to 23 copies per blood spot by year’s end. The Israeli SCID screening algorithm and the rate of positive results with different cutoffs are reviewed elsewhere ( 23 ). In 561 instances (0.3%), a second Guthrie card was requested following an initial positive result.…”

Universal Newborn Screening for Severe Combined Immunodeficiency (SCID)

“…Outside the US, routine TREC screening is currently performed in Israel, New Zealand, Norway, Taiwan, several provinces in Canada, Switzerland, Germany, Iceland, Sweden, Italy (Tuscany), Spain (Catalunia) and in some regions in Australia. In Israel, 290,864 children were screened between 2015 and 2017 and 13 patients with SCID were identified (~1 in 22,000) (13) whereas only 7 SCID patients were identified between 2010 and 2017 in Taiwan, where 920,398 children were screened (~1 in 131,000). This illustrates a broad range in incidence in the various countries (14).…”

Translating Molecular Technologies into Routine Newborn Screening Practice

“…By the end of 2018, all NBS programs in the United States had added SCID to their NBS panels, and the experience of NBS for SCID in 11 screening programs throughout the United States was reported in 2014 [ 14 , 15 ]. Progress in population-based NBS for SCID has also been made in many other countries, including Saudi Arabia, Spain, France, Sweden, the Netherlands, Taiwan, Brazil, Japan, and Israel [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ].…”