Newborn screening for spinal muscular atrophy followed by prompt SMA-specific treatment allowed pre-symptomatically treated patients to remain asymptomatic, whereas untreated children died or developed weakness.
Cohort (n=43)
Yes
Does newborn screening and prompt SMA-specific treatment improve neurodevelopmental outcomes in infants with spinal muscular atrophy?
Newborn screening for spinal muscular atrophy enables early, pre-symptomatic treatment which substantially improves neurodevelopmental outcomes and prevents early mortality.
BACKGROUND: Spinal muscular atrophy (SMA) is the most common neurodegenerative disease in childhood. Since motor neuron injury is usually not reversible, early diagnosis and treatment are essential to prevent major disability. Our objective was to assess the impact of genetic newborn screening for SMA on outcome. METHODS: We provided clinical data from 43 SMA patients, identified via polymerase chain reaction of the SMN1 gene from dried blood spots between January 2018 and January 2020 in Germany. Follow-up included neurophysiological examinations and standardized physiotherapeutic testing. RESULTS: Detection of SMA with newborn screening was consistent with known incidence in Germany. Birth prevalence was 1:6910; 39.5% had 2 SMN2 copies, 23% had 3 SMN2 copies, 32.5% had 4 copies, and 4.5% had 5 copies of the SMN2 gene. Treatment with SMA-specific medication could be started at the age of 14-39 days in 21 patients. Pre-symptomatically treated patients remained throughout asymptomatic within the observation period. 47% of patients with 2 SMN2 copies showed early, presumably intrauterine onset of disease. These patients reached motor milestones with delay; none of them developed respiratory symptoms. Untreated children with 2 SMN2 copies died. Untreated children with 3 SMN2 copies developed proximal weakness in their first year. In patients with ≥ 4 SMN2 copies, a follow-up strategy of "watchful waiting" was applied despite the fact that one of them was treated from the age of 6 months. Two infant siblings with 4 SMN2 copies were identified with a missed diagnosis of SMA type 3. CONCLUSION: Identification of newborns with infantile SMA and prompt SMA-specific treatment substantially improves neurodevelopmental outcome, and we recommend implementation in the public newborn screening in countries where therapy is available. Electrophysiology is a relevant parameter to support the urgency of therapy. There has to be a short time interval between a positive screening result and referral to a therapy-ready specialized treatment center.
Vill et al. (Wed,) conducted a cohort in Spinal muscular atrophy (SMA) (n=43). Newborn screening and prompt SMA-specific treatment (Nusinersen) vs. Untreated patients (natural history) was evaluated on Neurodevelopmental outcome and symptom onset. Newborn screening for spinal muscular atrophy followed by prompt SMA-specific treatment allowed pre-symptomatically treated patients to remain asymptomatic, whereas untreated children died or developed weakness.