Journal
GENETICS IN MEDICINE
Volume 26, Issue 1, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.gim.2023.101009
Keywords
Creatine kinase-MM; DMD; Duchenne muscular dystrophy; Gene panel; Newborn screening
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Screening for elevated CK-MM levels in dried blood spots is a feasible method to identify newborns with DMD. Including specific cutoffs, repeat testing, and genetic sequencing can improve the accuracy and sensitivity of screening.
Purpose: Current and emerging treatments for Duchenne muscular dystrophy (DMD) position DMD as a candidate condition for newborn screening (NBS). In anticipation of the nomination of DMD for universal NBS, we conducted a prospective study under the Early Check voluntary NBS research program in North Carolina, United States.Methods: We performed screening for creatine kinase-MM (CK-MM), a biomarker of muscle damage, on residual routine newborn dried blood spots (DBS) from participating newborns. Total creatine kinase testing and next generation sequencing of an 86-neuromuscular gene panel that included DMD were offered to parents of newborns who screened positive. Bivariate and multivariable analyses were performed to assess effects of biological and demographic predictors on CK-MM levels in DBS.Results: We screened 13,354 newborns and identified 2 males with DMD. The provisional 1626 ng/mL cutoff was raised to 2032 ng/mL to improve specificity, and additional cutoffs (900 and 360 ng/mL) were implemented to improve sensitivity for older and low-birthweight newborns.Conclusion: Population-scale screening for elevated CK-MM in DBS is a feasible approach to identify newborns with DMD. Inclusion of birthweight- and age-specific cutoffs, repeat creatine kinase testing after 72 hours of age, and DMD sequencing improve sensitivity and specificity of screening.(c) 2023 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics. This is an open access article under the CC BY-NC-ND license
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