Neonatal screening for severe combined immunodeficiency

Abstract

Population-based newborn screening for severe combined immunodeficiency (SCID) and related disorders has been instituted in five states, with several more planning to add this testing to their newborn screening panels. This review summarizes the rationale, development and implementation of SCID screening programs to date and highlights current and future challenges. Early results of T-cell receptor excision circle (TREC) testing newborns in pilot states indicate that this addition to the newborn screening panel can be successfully integrated into state public health programs. The TREC test has clinical validity and TRECs, as predicted, are an excellent biomarker of poor T lymphocyte production in the thymus or increased lymphocyte loss resulting in T-cell lymphopenia. A variety of cases with typical SCID genotypes and other conditions have been detected in a timely manner and referred for appropriate early treatment. Early detection of primary immunodeficiency is recognized as important for avoiding infectious complications that compromise outcomes. Routine screening of all newborns with the TREC test, implemented as part of an integrated public health program, can achieve presymptomatic diagnosis of SCID and other disorders with T-cell lymphopenia, allowing prompt and effective treatment and leading to a better understanding of the spectrum of these disorders and how to manage them.