BACKGROUND: Severe combined immunodeficiency (SCID) is a fatal but treatable inborn error of immunity (IEI). Newborn screening (NBS) using T-cell receptor excision circles (TREC) has been adopted globally, with very few countries incorporating kappa recombination excision circles (KREC) to also detect early B-cell development disorders, such as X-linked agammaglobulinemia (XLA). OBJECTIVE: To evaluate the effectiveness of a 2-year pilot SCID NBS program in the Czech Republic, emphasising the utility of combined TREC/KREC screening. METHODS: Between January 2022 and December 2023, a dual TREC/KREC NBS pilot was conducted across the Czech Republic, alongside spinal muscular atrophy (SMA) screening. Approximately 200,000 newborns were screened using quantitative real-time PCR on dried blood spots collected 48-72 h after birth. RESULTS: The pilot referred 58 newborns, identifying 21 cases of IEI, including two SCID cases, with an overall incidence of TREC/KREC screenable IEI of 10.5/100,000 newborns. SCID incidence was 1/100,000. KREC screening proved invaluable, detecting 10 cases of congenital agammaglobulinemia including novel non-XLA forms, which increased the estimated incidence of agammaglobulinemia in the Czech Republic sixfold. Over one-third of low KREC results were linked to maternal immunosuppression. CONCLUSION: The Czech pilot demonstrated the effectiveness of integrated TREC/KREC NBS in detecting both T- and B-cell immunodeficiencies. As of 2024, SCID and SMA screening are included in the nationwide NBS, with KREC screening significantly improving early detection of B-cell disorders.

Centre for Cardiovascular Surgery and Transplantation Brno Czech Republic

Centre for Molecular Biology and Gene Therapy Internal Haematology and Oncology Clinic University Hospital Brno Brno Czech Republic

CLIP Childhood Leukaemia Investigation Prague Prague Czech Republic

Department of Biology and Medical Genetics 2nd Faculty of Medicine Charles University and University Hospital Motol Prague Czech Republic

Department of Clinical Immunology and Allergology Faculty of Medicine Masaryk University and St Anne's University Hospital Brno Czech Republic

Department of Immunology 2nd Faculty of Medicine Charles University and University Hospital in Motol Prague Czech Republic

Department of Pediatric Hematology and Oncology 2nd Faculty of Medicine Charles University and University Hospital in Motol Prague Czech Republic

Department of Pediatrics University Hospital Brno Brno Czech Republic

Diagnostic Laboratories of Inherited Metabolic Disorders Department of Pediatrics and Inherited Metabolic Disorders 1st Faculty of Medicine Charles University and General University Hospital Prague Prague Czech Republic

Faculty of Medicine Masaryk University Brno Czech Republic

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