Spinal muscular atrophy (SMA) is an autosomal recessive condition characterized by alpha motor neuron degeneration in the spinal cord anterior horn. Clinical symptoms manifest in the first weeks to months of life in the most severe cases, resulting in progressive symmetrical weakness and atrophy of the proximal voluntary muscles. Approximately 95% of SMA patients present with homozygous deletion of the SMN1 gene. With multiple available therapies preventing symptom development and slowing disease progression, newborn screening for SMA is essential to identify at-risk individuals. From 2018 to 2023, a total of 239,844 infants were screened. 13 positive screens were confirmed to have SMA. An additional case was determined to be a false positive. We are not aware of any false-negative cases. All patients were seen promptly, with diagnosis confirmed within 1 week of the initial clinical visit. Patients were treated with nusinersen or onasemnogene abeparvovec. Treated patients with two copies of SMN2 are meeting important developmental milestones inconsistent with the natural history of type 1 SMA. Patients with 3–4 copies of SMN2 follow normal developmental timelines. Newborn screening is an effective tool for the early identification and treatment of patients with SMA. Presymptomatic treatment dramatically shifts the natural history of SMA, with most patients meeting appropriate developmental milestones. Patients with two copies of SMN2 identified through newborn screening constitute a neurogenetic emergency. Due to the complexities of follow-up, a multidisciplinary team, including close communication with the newborn screening program, is required to facilitate timely diagnosis and treatment.

Objective: To document the reliability, validity and sensitivity of the FSHD Composite Outcome Measure Background: Standardized clinical outcome assessments may serve as endpoints for late phase FSHD clinical trials. The FSHD-COM is a 13 item composite measure that assesses the functional impact of the disease by measuring areas that have been identified as meaningful to individuals with FSHD. Design/Methods: Individuals with FSHD participating in the multi-site, international ReSolve Study were assessed using the FSHD-COM at baseline, 3, 12, 18 and 24 months. The FSHD-COM was performed twice over consecutive days at baseline to examine the test-retest reliability. Manual muscle testing (MMT) and the FSHD Clinical Score were also performed to examine validity. Longitudinal analyses will be used to examine the change over time of the FSHD-COM items and total score. Results: 237 participants (56% male) with a mean age of 50.3 (range 19–75) years completed baseline assessments. The interclass correlation coefficient for the total FSHD-COM score was 0.98 with individual items ranging from 0.85–0.99. The FSHD-COM score was correlated to overall MMT (ρ=0.89; p=0.001) and the FSHD clinical score (ρ=0.82; p=0.001). Change in the FSHD-COM score at 12, 18 and 24 months will be presented. Conclusions: The FSHD-COM score can be administered reliably in a multi-site study. Concurrent validity is supported by the correlations between the FSHD-COM score and measures of disease severity. The final analysis examining the responsiveness will be discussed. Disclosure: Ms. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Fulcrum. Ms. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Avidity. Ms. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for DyneTherapeutic. Ms. Eichinger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche. Ms. Eichinger has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for FSHD Society. The institution of Ms. Eichinger has received research support from Charcot Marie Tooth Association. Michael McDermott has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for NeuroDerm, Ltd.. Michael McDermott has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly and Company. Michael McDermott has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Catabasis Pharmaceuticals, Inc.. Michael McDermott has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vaccinex, Inc.. Michael McDermott has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurocrine Biosciences, Inc.. Michael McDermott has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Prilenia Therapeutics Development, Inc.. Michael McDermott has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for ReveraGen BioPharma, Inc.. Michael McDermott has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for NS Pharma, Inc.. The institution of Michael McDermott has received research support from NIH. The institution of Michael McDermott has received research support from FDA. The institution of Michael McDermott has received research support from Cure SMA. Kiley Higgs has nothing to disclose. Miss Walker has nothing to disclose. Leann Lewis has nothing to disclose. William Martens has nothing to disclose. The institution of Dr. Leung has received research support from US Department of Defense. The institution of Dr. Leung has received research support from Fulcrum Therapeutics. The institution of Dr. Leung has received research support from ML Bio Solutions, Inc.. The institution of Dr. Leung has received research support from Sarepta Therapeutics. The institution of Dr. Leung has received research support from Cumberland Pharmaceuticals. The institution of Dr. Leung has received research support from FibroGen Inc.. The institution of Dr. Leung has received research support from Astellas Pharma. The institution of Dr. Leung has received research support from University of Kansas Medical Center Research Institute. The institution of Dr. Leung has received research support from Pfizer, Inc.. The institution of Dr. Leung has received research support from Genethon. The institution of Dr. Leung has received research support from Harmony Biosciences. The institution of Dr. Leung has received research support from Edgewise Therapeutics. Nikia Stinson has nothing to disclose. Dr. Holzer has received personal compensation for serving as an employee of Kennedy Krieger Institute. Dr. Sacconi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for DYNE THERAPEUTICS. Dr. Sacconi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LUPIN. Dr. Sacconi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BIOGEN. Dr. Sacconi has received personal compensation in the range of $500-$4,999 for serving as a Consultant for LFB. Dr. Sacconi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for ROCHE. Dr. Sacconi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for...