Newborn Screening for Severe Combined Immunodeficiency

Abstract

Newborn screening (NBS) for Severe Combined Immunodeficiency (SCID) has been successfully implemented in all 50 United States and Puerto Rico from 2008-2018. This life-saving screening tool has drastically improved overall survival of babies diagnosed with SCID from 74% to 96%. TREC is a stable, circular DNA molecule that is produced during the process of T-cell receptor (TCR) rearrangement and is the target of the quantitative PCR screen on Guthrie cards. Low TRECs are a marker of low naive T cell numbers. This new screening process has facilitated discovery of new genes that cause SCID, new data on patients with SCID, as well as other causes of infant lymphopenia. This new information has prompted the Primary Immune Disease Treatment Consortium to re-classify the diagnosis of SCID in 2022. Providers who are first recipients of a positive screen must understand laboratory methods of the screen, treatment recommendations and options for those with SCID as well as other relevant causes of a positive screen such as 22q11 syndrome, Ataxia Telangiectasia, prematurity. These topics are crucial to cover when reporting results to a family who is receiving unexpected news on their otherwise well appearing newborn. Prompt medical evaluation and prophylaxis have been shown to improve survival and outcomes, and providers play an essential role in relaying this information and care to families. While TREC screen has proven to be a valuable screening tool for conditions with lymphopenia, over 500 immune deficiency diseases exist, and expansion to include these diseases on the NBS could be possible with Next Generation Sequencing in the future.