Five Years of Combined Newborn Screening Quantifying TREC and KREC in Switzerland

Background Since January 1, 2019, T-cell receptor (TREC) and kappa-deleting recombination excision circles (KREC) have been measured as a part of the Swiss newborn screening program.Objective To summarize key findings from the program's first 5 years and assess the added value and burden of KREC measurement.Methods Analysis of data from the Swiss prospective newborn screening registry cohort, 2019-2023, was performed.Results A total of 435,985 newborns were screened, of whom 409 (0.09%) had abnormal results. Among these, 386 (94%) were enrolled in the study. Of the participants, 181 (47%) had abnormal TREC levels (with or without abnormal KREC), and 205 (53%) had isolated abnormal KREC levels. Within the abnormal TREC group, 11 newborns were diagnosed with severe combined immunodeficiency (SCID), and 2 with congenital athymia. An additional 41 newborns had milder T-cell deficiencies. Among those with abnormal KREC levels, 8 were diagnosed with agammaglobulinemia and 1 with ataxia telangiectasia. Transiently abnormal TREC levels were most commonly associated with prematurity, low birth weight, inpatient treatment, and conditions such as congenital heart disease, infections, and syndromic disorders (eg, trisomy 21 and Noonan syndrome). Transiently abnormal KREC levels were predominantly linked to maternal immunosuppressive therapy. The overall referral rate remained low (0.025%), with KREC accounting for only one-fifth of all referrals.Conclusions The Swiss newborn screening program successfully identified cases of SCID, congenital athymia, moderate T-cell deficiencies, and agammaglobulinemia during its first 5 years. The combined method is feasible, and inclusion of KREC leads to only a modest increase in referrals.