Severe Combined Immunodeficiency in the Newborn Period

Severe combined immunodeficiency (SCID) is a rare and life-threatening disease, characterized by an intrinsic defect of the hematopoietic stem cell that disrupts appropriate T lymphocyte maturation. Previously, early diagnosis of SCID used to require an experienced physician who identified patients with abnormal absolute lymphocyte count and distinct clinical manifestations. Over the past few decades, the implementation of universal newborn screening has enhanced our diagnostic capabilities. The Pediatric Immune Deficiency Treatment Consortium updated the definitions of SCID in 2022, providing a comprehensive approach to differentiate patients with typical SCID from leaky or atypical SCID, and Omenn syndrome from those without SCID. SCID is caused by multiple genetic abnormalities with different phenotypes involving T cells and possibly natural killer cells, and B cells. The management of patients with SCID requires a multifocal approach with early interventions to prevent infections and the concurrent planning of a curative therapy such as hematopoietic stem cell transplantation or, in some cases, gene therapy. Early intervention in affected patients with the absence of infection is a predictor of good long-term outcomes, but because of evolving bone marrow transplant and gene therapy techniques, patients need to be monitored long term to assess for possible late side effects. This review will focus on the most common genetic causes of SCID and their distinct characteristics, acute management, and curative options.