Newborn screening for severe congenital immunodeficiencies represents an important step toward the early identification of children with potentially life-threatening immune disorders. In Slovenia, screening for severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) has been implemented since March 2024 using quantification of T cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs) from dried blood spot samples.
Since implementation, approximately 30,000 newborns have been screened. No confirmed positive TREC screening results were observed among term newborns. Most abnormal results were associated with prematurity and related complications. Several extremely premature infants showed low TREC values requiring careful follow-up; subsequent evaluation demonstrated normalization of TREC levels over time and preserved cellular immunity.
KREC screening identified 15 children with abnormal results. Further evaluation showed that reduced KREC levels were frequently associated with maternal immunosuppressive therapy or viral infections during pregnancy. Five children presented with absent or markedly decreased KREC values and required additional immunological assessment.
Prior to the implementation of TREC/KREC screening, expanded newborn screening for inherited metabolic disorders was introduced in Slovenia in September 2018. The program uses tandem mass spectrometry (MS/MS) to detect a broad spectrum of inborn errors of metabolism. This program has also contributed to the identification and further evaluation of rare metabolic conditions associated with immune dysfunction, including adenosine deaminase (ADA) deficiency. Through this approach, we identified a patient with suspected ADA deficiency. Genetic testing revealed a previously described pathogenic variant together with an additional likely pathogenic variant, without definitive functional confirmation.
The child received antimicrobial prophylaxis and immunoglobulin replacement therapy during the first year of life. Despite markedly reduced enzyme activity, the child demonstrated normal development, adequate immune responses, and appropriate recovery from infections. Repeated TREC/KREC screening in this patient was normal.
The Slovenian experience emphasizes the importance of appropriate interpretation of newborn screening results, particularly in premature infants. Integration of laboratory findings with clinical evaluation and genetic data is essential for accurate diagnosis and management of children with suspected primary immunodeficiencies.
