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Evidence-based path to newborn screening for Duchenne muscular dystrophy
Jerry R Mendell1, Chris Shilling, Nancy D Leslie
1Department of Pediatrics, Ohio State University and Nationwide Children's Hospital, Columbus, OH 43205, USA. Jerry.Mendell@nationwidechildrens.org
Annals of Neurology
|March 28, 2012
Summary
A new two-tier system for newborn screening effectively identifies Duchenne muscular dystrophy (DMD) by analyzing creatine kinase (CK) levels in dried blood spots, reducing false positives.
Area of Science:
- Biochemistry
- Genetics
- Neonatal screening
Background:
- Elevated creatine kinase (CK) levels in newborn dried blood spots are common due to the birthing process.
- CK is a marker in newborn screening, but elevated levels can lead to false positives for Duchenne muscular dystrophy (DMD).
Purpose of the Study:
- To introduce and validate a two-tier system for newborn screening of DMD using dried blood spots.
- To minimize false-positive results in newborn screening for DMD.
Main Methods:
- A fluorometric assay measured CK activity in 30,547 dried blood spot samples to establish population-based ranges.
- Genomic DNA from dried blood spots underwent whole genome amplification and multiplex ligation-dependent probe amplification for DMD gene mutation analysis.
Main Results:
- DMD gene mutations (exonic deletions) were identified in 6 of 37,649 males, all with CK levels >2,000 U/L.
- In 3 newborns with CK >2,000 U/L but no DMD mutations, mutations in limb-girdle muscular dystrophy genes (DYSF, SGCB, FKRP) were found.
Conclusions:
- A two-tier analysis system for newborn screening of DMD has been successfully established.
- This screening approach is suitable for healthcare systems, reduces false positives, and uses CK levels to predict DMD gene mutations.
