589 - Utility and Feasibility of Universal Newborn Screening for Duchenne Muscular Dystrophy Using CK-MM on Dried Blood Spot

Publication Number: 3570.589

Rebecca J. Wilson, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Olivia D'Annibale, University of Cincinnati College of Medicine, Cincinnati, OH, United States; Nancy D. Leslie, Cincinnati Children's Hospital Medical Center, Cincinnati Children's Hospital, OH, United States; Jonathan L. Slaughter, Nationwide Children's Hospital and The Ohio State University, Columbus, OH, United States; Henry T. Akinbi, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, United States; Mari Mori, Emory University School of Medicine, Atlanta, GA, United States

Background: Reliance of clinical diagnosis of dystrophinopathies (DMD) results in delay which contributes to poor long-term outcomes, with respect to shorter life expectancy and poor quality of life. The advent/implementation of newborn screening (NBS) for DMD offers hope for earlier initiation of therapies and for better prognosis. Ohio Department of Health (ODH) instituted a single-tier NBS for DMD with CK-MM on dried blood spots on all babies in April 2024.

Objective: To analyze CK-MM data from universal NBS for DMD in Ohio state, the first state to implement NBS for DMD, in order to establish cutoffs that will maximize detection (true positives) and minimize false negatives.

Design/Methods: Deidentified data from the first year of implementation of NBS for DMD were analyzed to determine birth prevalence, trends in CK-MM relative to time of collection, gestational age and negative predictive accuracies for cutoffs at 99, 99.5, and 99.9th percentiles, using R studio.

Results: A total of 156,838 CK-MM data from 152,571 babies were analyzed. Of this data, 148,751 babies had only an initial NBS CKMM performed while 3,663 babies had an initial and repeat NBS CK-MM performed. Of the initial NBS data, 146,791 babies were within normal range and 5,603 babies were inconclusive, per ODH current criteria. CK-MM concentrations were highest in specimens collected at < 48 h of age and correlated with the gestational age. There was no significant difference between concentrations in males (mean, 394 U/ml) vs female (364) babies. Six babies reported as inconclusive CK-MM for initial NBS testing were diagnosed with DMD in the cohort following genetic/molecular testing. Percentile cutoffs for CKMM concentrations were calculated based on the dataset for each weight group and age at collection. A cutoff of 2079 U/ml (99.5th percentile) in specimens collected at < 48 h identified all 6 affected babies and one baby with non-DMD muscular dystrophy. Birth prevalence of DMD in our cohort was 4 per 100,000.

Conclusion(s): Our findings support the feasibility and utility of implementing CK-MM as a first-tier analyte for screening for DMD to enable presymptomatic detection of affected infants, and allow expeditious confirmatory testing with gene sequencing, which will prompt early intervention. A cutoff of 2000 U/ml will identify babies with DMD without incurring unacceptable false positives. Prospects for early intervention will be greatly enhanced with NBS for DMD.

Table 1
CK-MM concentrations (ng/mL) by weight (g) for initial newborn screening. N, number of patients; Age Group, Age in hours of blood sample collection.