Newborn Screening for SMA - Results After Two Years of a Large Pilot Project 

Abstract Background: Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. Since motor neuron injury is mostly not reversible, early diagnosis and treatment are essential to prevent major disability. The aim of this study was to assess the impact of newborn screening (NBS) for SMA on clinical outcome. Methods: The pilot project started in January 2018 in Germany and is still ongoing. Genetic screening via PCR of the SMN1 gene from dried blood spots was implemented in the routine NBS structure. Follow-up included neurophysiological examinations, CHOP INTEND and HINE-2.Results: Among 297,163 screened children, 43 cases of SMA were identified, resulting in an incidence of 1:6910. In 21 patients with ≤3 SMN2 copies, treatment with nusinersen according to the FDA/EMA guidelines was started age 14-39 days. Median follow-up period, regarding motor milestones was 12.3 months (range 1.5-26 months). All pre-symptomatically treated patients remained asymptomatic as far as age at last examination already allows this statement. 41% of patients with 2 SMN2 copies had already early, mostly subtle signs of disease. These patients reached motor milestones, however with a certain delay. None developed respiratory symptoms. Two untreated patients with 2 SMN2 copies died. Four untreated patients with 3 SMN2 copies, one of whom was initially diagnosed with 4 SMN2 copies by a different method, developed proximal weakness at ages 6-11 months. Two siblings of babies with 4 SMN2 copies were identified with a missed diagnosis of SMA 3. Conclusion: Identification of newborns with infantile SMA improves neurodevelopmental outcome enormously. It should be introduced in all countries where therapy is available. Detection of SMA via NBS did not increase the incidence compared to the known incidence rate. Early treatment of patients with 4 SMN2 copies should be considered.