PC1100: Understanding Time to Treat and Motor Milestone Achievement in a Cohort of Individuals with Spinal Muscular Atrophy Identified via Newborn Screening

Background: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease due to a mutation in or deletion of the SMN1 gene, resulting in the destruction of motor nerve cells. Early intervention is imperative to slow disease progression. In 2018, SMA was added to the US federal Recommended Uniform Screening Panel. As of 3/2022, 44 states are screening for SMA. The objective of this analysis was to understand diagnostic/treatment delay and age at motor milestone achievement in a cohort of individuals with SMA that were identified via newborn screening (NBS).

Methods: This was a retrospective analysis of the Cure SMA Newborn Screening Registry (NBSR) data, composed of consented parent/caregiver reported data used to track the outcomes of individuals with SMA identified via NBS. All individuals that were part of the NBSR as of 3/2022 were included in this analysis.

Results: 57 individuals with SMA participated in the NBSR. The median age at survey completion was 211 days, and 54.4% of individuals were female. The median age at diagnosis confirmation was 7 days (range: 1‒22 days). Half of the individuals had two copies of SMN2 (51.8%), followed by three copies (26.8%), four or more copies (14.3%), and one copy (7.1%). Ninety-four percent of individuals did not have symptoms at birth. 80% of individuals received treatment, and median age at first treatment was 28 days. When stratified by SMN2 copy number, median age at treatment was closely related to SMN2 copy number and ranged from 27 days (1 copy) to 42 days (≥4 copies). Median time from diagnosis to first treatment was 19.5 days, and when stratified by SMN2 copy number, ranged from 15 days (1 copy) to 37 days (≥4 copies). Most parents/caregivers reported the affected individual reached at least one milestone at the time of survey completion (79%). The median age for individuals to hold their head up was 3 months (n=40). Median age to roll from back to stomach (n=30), roll from stomach to back (n=28), and sit supported (n=31) was 5 months. The median age to sit independently was 7 months (n=25) and to walk 14 months (n=7).

Conclusion: Newborn screening facilitates early identification, and, therefore, early intervention and treatment for infants with SMA. In this NBS cohort, both diagnosis and first treatment occurred within one month of life (median age of 7 and 28 days, respectively). Diagnosis age is much younger in this analysis than what is generally reported in literature for the general SMA population prior to newborn screening implementation (5-98 months). Additionally, median ages for achieving milestones are within published ranges for normal development. While limited by its small sample size, this analysis provides additional evidence for the impact of early diagnosis and intervention for individuals with SMA.