Nationwide Pilot Newborn Screening for Spinal Muscular Atrophy and Primary Immunodeficiencies in Greece

Newborn screening for primary immunodeficiencies and spinal muscular atrophy (SMA) enables early identification of infants at risk for severe disorders, facilitating timely treatment and improved outcomes. This study describes the first Greek experience with combined screening for T-cell receptor excision circles (TREC), kappa-deleting recombination excision circles (KREC), and SMN1 using a single dried blood spot (DBS) sample. During 2026, 29.460 newborns were screened using a commercially available in vitro diagnostic kit. TREC and KREC were assessed semi-quantitatively, while SMA screening was based on qualitative detection of the SMN1 exon 7 target. Of these, 2.168 (7,36%) required duplicate retesting, with 481 requiring a second DBS sample. Among the 481 newborns for whom a second DBS card was requested, 469 cards were received. Of these, 446 were classified as negative, 13 remained inconclusive, 4 were referred for genetic/immunological confirmatory evaluation, 2 remained under immunological follow-up, and 4 demonstrated recovery on repeat testing. Confirmatory evaluation identified four clinically significant cases: two with SMA, one with severe T-cell lymphopenia associated with 22q11.2 deletion syndrome, and one with CHARGE syndrome. Several low TREC/KREC results normalized on repeat testing. This experience demonstrates the feasibility of combined screening and highlights the importance of appropriate follow-up and confirmatory evaluation.