T-Cell Receptor Excision Circle/Kappa-Deleting Recombination Excision Circle-Based Newborn Screening Program for Severe Combined Immunodeficiency in Kumamoto, Japan

Severe combined immunodeficiency (SCID) is a life-threatening hereditary disorder that requires early diagnosis and intervention. Therefore, this study aimed to evaluate the utility of T-cell receptor excision circle (TREC) and kappa-deleting recombination excision circle (KREC) measurements in newborn screening (NBS) for SCID and other primary immunodeficiencies in Kumamoto Prefecture, Japan. In a TREC-based NBS program (February 2019–March 2022, N = 43,658), six newborns (0.014%) underwent immunological testing, and three (0.007%) were diagnosed with T-cell lymphopenia. In a subsequent combined TREC/KREC-based NBS program (April 2022–March 2023, N = 12,335), eight newborns (0.065%) required further testing, and one (0.008%) was diagnosed with X-linked agammaglobulinemia. Decreased KREC levels were observed in two newborns exposed to maternal azathioprine (AZP). The TREC levels tended to be lower in more premature infants, whereas the KREC levels showed no clear correlation with gestational age (GA). Both the TREC and KREC levels were reduced in infants with low birth weights (BWs). These findings indicate that the combined TREC/KREC-based NBS program is an effective approach for detecting T- and B-cell immunodeficiencies. However, clinical factors such as maternal AZP exposure, low GA, and low BW may affect TREC and/or KREC levels, necessitating careful interpretation of results from dried blood spot samples.