Immunodeficiency: Severe Combined Immunodeficiency Disease

Abstract

Severe combined immunodeficiency disease (SCID) is defined as (1) absence or very low number of T cells (<300 CD3 + T cells/mm 3 ) and no or very low T‐cell function (<10% of lower limit of normal) as measured by response to phytohaemagglutinin or (2) presence of T cells of maternal origin. It has an incidence of approximately 1 per every 58 000 live births. SCID is caused by defects in at least 16 different genes, each of which results in failure to produce functional host‐derived T cells through various pathogenic mechanisms. Improved understanding of these fundamental processes has led to significant advances in the diagnosis, management and definitive treatment of individuals with this life‐threatening condition. Key Concepts Severe combined immunodeficiency disease is defined by a congenital lack of functional T cells, resulting in death from infections by 1–2 years of age. Many molecular defects underlying SCID have been identified, yielding valuable insights regarding immune biology. Diagnosis has been enhanced by newborn screening, resulting in successful treatment of affected infants. Definitive therapy options include haematopoietic stem cell transplantation and gene therapy, the latter of which has shown promise and remains actively investigated. Optimal outcomes have been associated with definitive treatment before 3.5 months of age and onset of active infections.