Neonatal screening of severe combined immunodeficiencies

Severe combined immunodeficiencies (SCID) are a group of inherited diseases of the immune system characterized by profound abnormalities of T-cell development. Infants with SCID require prompt clinical intervention to prevent life-threatening infection and studies show significantly improved survival in babies diagnosed at birth based on previous family history. SCID follows the criteria for population-based newborn screening because it is asymptomatic at birth and fatal within the 1st year of life if there is no intervention, the confirmation of the disease is easy, there is a curative treatment, and it is known that early hematopoietic stem cell transplantation significantly improves survival, the quality of immune reconstitution, and quality of life. Quantification of T-cell receptor excision circles (TRECs) in DNA extracted from Guthrie samples is a sensitive and specific screening test for SCID. We conducted a nationwide prospective study of neonatal screening of SCID in a population of 200,000 French newborns over a period of 2 years. The objective was to study the clinical utility and the cost-effectiveness ratio, and to demonstrate that universal SCID screening could result in a substantial benefit to detect individuals, making screening relatively cost-effective in spite of the low incidence of the disease.