Neonatal screening for Duchenne muscular dystrophy in eastern China: a closed prospective study

Duchenne muscular dystrophy (DMD) is a progressive, lethal X-linked neuromuscular disorder with a worldwide incidence of 1:5,000. The early identification of DMD through newborn screening (NBS) has gained increased attention and interest due to the availability of new therapies. The study aimed to determine the analytical and clinical validity of screening for the muscular isoenzyme form of creatine kinase (CK) to identify newborns at risk for DMD using dried blood spots (DBSs) collected from a routine part of NBS. We also collected data on the prevalence of DMD in newborns in Zhejiang, China.

A closed concurrent cohort study for Duchenne was introduced at The Children's Hospital Zhejiang University School of Medicine, China. Over an eight-month period, DBSs from the 42,862 male infants enrolled in the study were collected and tested for elevated CK using a prototype Genetic Screening Platform (GSP^®) Neonatal creatine kinase-muscle isozyme (CK-MM) assay following parental consent.

A total of 214 male infants had elevated CK-MM activity >400 ng/mL (~99.5th percentile). Eighty-six percent (184) of infants returned for further testing; 174 infants had normal serum CK, and ten infants had elevated serum CK. DMD was confirmed in eight patients by next-generation sequencing (NGS) of the DMD gene. Among the 30 patients that were lost to follow-up, DMD was confirmed in 3 by NGS. In total, 11 infants were diagnosed with DMD or Becker muscular dystrophy (BMD). Further examination of the cut-off value indicated that a CK-MM >700 ng/mL (~99.9th percentile) correctly identified all confirmed patients. Genetic testing could not be performed on all samples to more accurately verify the detection efficiency of CK-MM assay screening.

This study successfully provides preliminary performance data for clinical application of the CK-MM assay as an NBS for DMD.