Two Years of Newborn Screening for Severe Combined Immune Deficiency in Western Australia

Introduction Population-based screening for severe combined immune deficiency (SCID) recently commenced in Western Australia using the newborn bloodspot screening sample to quantify T cell receptor excision circles (TRECs) and kappa-depleting recombination excision circles (KRECs). These are surrogate markers for naïve T and B lymphocytes, respectively. The primary aim is early detection of infants with SCID; however, other clinically significant T and B cell lymphopenias are also identified. Method All infants with confirmed decreased or absent TRECs and/or absent KRECs were referred to Western Australia’s sole tertiary paediatric immunology service since commencement of screening, May 1, 2023 to May 1, 2025. TREC and KREC values, together with corresponding flow cytometry results, were matched to the final outcome or diagnosis for each infant where available. Results Our service received 15 referrals from 60,048 live births in the two-year time period. These were for undetectable TRECs in 47% (7/15), decreased TRECs in 33% (5/15), and undetectable KRECs in 20% (3/15). Of the 7 infants with undetectable TRECs, 3 cases were identified with SCID, 2 were classical SCID, and 1 was atypical SCID. All 3 infants progressed to a haematopoietic stem cell transplant (HSCT). 1 infant with undetectable TRECs and 3 infants with decreased TRECs had a diagnosed or presumed congenital syndrome consistent with absent or decreased TRECs. Congenital agammaglobulinaemia was confirmed in 2/3 infants referred with undetectable KRECs; both required immunoglobulin replacement therapy. Conclusion Since commencing, our SCID newborn screening program has identified 3 cases of SCID, approximately 1:20,000 live births. The early identification of these infants with SCID has led to timely HSCT, whilst detection of non-SCID causes of T and B cell lymphopenia has expedited diagnosis and facilitated early treatment in clinically significant conditions.