Effects of newborn screening and nusinersen on survival and functional outcomes in spinal muscular atrophy with two SMN2 copies: A nationwide multicentre real-world study from Turkey.

Spinal muscular atrophy (SMA) Type 1 in infants with two SMN2 copies is characterised by rapid motor neuron loss and a historically fatal course if untreated; however, nationwide real-world comparative data evaluating screening efficacy remain scarce. This nationwide retrospective, multicentre study evaluated the real-world impact of Turkey's national newborn screening (NBS) program on clinical outcomes in a high-risk population-of infants with genetically confirmed SMA and two SMN2 copies-treated with nusinersen. Patients were classified into a historical symptomatic cohort diagnosed before NBS implementation (pre-NBS, n = 162) and an NBS cohort identified through screening (n = 96); all received nusinersen. Outcomes included survival, respiratory and nutritional independence, and acquisition of WHO-defined motor milestones. Motor function was evaluated using the Children's Hospital of Philadelphia-Infant Test of Neuromuscular Disorders (CHOP-INTEND) scale. The NBS program markedly reduced the mean age at diagnosis and treatment initiation. Mortality was 6.3% in the NBS cohort compared with 30.9% in the pre-NBS group (p < 0.001). CHOP-INTEND scores at baseline were higher in the NBS cohort. Sustained motor gains were confirmed in both cohorts, though the NBS cohort maintained superior function throughout follow-up; 48.3% of NBS-identified infants achieved independent walking, compared with only 8.6% in the pre-NBS group. Preservation of bulbar and respiratory function was superior in the NBS cohort, whereas the pre-NBS group demonstrated progressive decline. NBS program fundamentally altered the clinical trajectory of SMA Type 1 in infants with two SMN2 copies in the present cohort. Pre-symptomatic treatment in the NBS cohort supports sustained motor development and preserves bulbar and respiratory functions, underscoring the importance of minimising delays between birth, diagnosis, and treatment initiation.