Primary immunodeficiency diseases (PID) are the latest addition to population-scale newborn screening (NBS) programs. PID are a group of inborn errors of immune defense function and can result in severe infectious complications already early in life. Children affected by severe combined immunodeficiencies (SCID) or agammaglobulinemia show a significant mortality and morbidity in the first year of life if not diagnosed and treated as early as possible.(1)

As therapeutic options, including stem cell transplantation, immunoglobulin substitution, enzyme replacement or gene therapy are widely available for affected patients, focus is on the efficient and rapid diagnosis of affected infants.(2)

Severe PID can be characterized by absence or low numbers of T- and B-lymphocytes in neonatal blood. Using polymerase chain reaction, it is possible to measure circular biomarkers of T- and B-cell differentiation, allowing screening for those newborns affected by severe PID.(3)