Five-year experience of a combined newborn screening for spinal muscular atrophy and severe combined immunodeficiency in Liguria, Italy

The combined newborn screening program for Spinal Muscular Atrophy (SMA) and Severe Combined Immunodeficiency (SCID) was evaluated in Liguria through a five-year pilot study involving 32,289 newborns. A single multiplex real-time PCR assay on dried blood spots enabled simultaneous detection of SMN1 exon 7 deletions and quantification of T-Cell Receptor Excision Circles (TREC) and Kappa-Deleting Recombination Excision Circles (KREC), achieving near-complete population coverage and a low recall rate. Ten newborns received a confirmed diagnosis of a targeted condition: five newborns were diagnosed with spinal muscular atrophy (SMA), of whom four were treated presymptomatically and achieved favorable clinical outcomes, whereas one with SMA type 0 died a few days after birth. Five newborns were diagnosed with immunodeficiencies, including two cases of adenosine deaminase (ADA)-related severe combined immunodeficiency (SCID), and three clinically significant secondary findings (idiopathic T-cell lymphopenia, DiGeorge syndrome, and transient B-cell lymphopenia). No false-negative cases were observed during follow-up. The TREC and KREC profiles were consistent with the underlying immunological diagnoses. Overall, the study demonstrates that combined SMA and SCID newborn screening is feasible, reliable, and clinically impactful, supporting its integration into public health screening programs.