[Update on the diagnosis and management of severe combined immunodeficiency].

Abstract

Severe combined immunodeficiency (SCID) is one of the most severe forms of inborn errors of immunity (IEI), characterized by profound defects in T-cell development and function. Without treatment, affected infants typically develop life-threatening infections and often die within the first year of life. Early diagnosis before the onset of infection is critical because timely curative treatment, such as hematopoietic cell transplantation, can markedly improve survival. In recent years, newborn screening (NBS) using T-cell receptor excision circles (TRECs) has enabled presymptomatic identification of SCID, leading to substantial changes in the clinical management of this disease. However, several challenges have emerged with the widespread implementation of NBS, including false-negative results in adenosine deaminase (ADA) deficiency and difficulties in interpreting TRECs-low results in patients with underlying conditions associated with impaired thymic function. In this review, we summarize the clinical features and pathophysiology of SCID and outline the principles and current status of NBS. We also present a case of X-linked SCID associated with Down syndrome to highlight diagnostic pitfalls and the importance of comprehensive evaluation for early diagnosis.