Comparison of Newborn Screening Platforms for Lysosomal Storage Disorders

This poster was presented at SLEIMPN 2019 in Buenos Aires, Argentina.

Authors: Deeksha S. Bali and David S. Millington, Department of Pediatrics-Medical Genetics, Duke University Medical Center, Durham, NC, USA

Two FDA-cleared platforms are currently available for lysosomal storage disorder (LSD) enzyme testing from dried blood spot specimens – tandem mass spectrometry (MS/MS) and digital microfluidic fluorometry (DMF).

Substantial data sets are available from the prospective LSD screening programs in the United States from the states of Missouri (N=441,000 infants screened using DMF) and Illinois (N=220,000 infants screened using MS/MS). The data sets do not show significant differences between the two testing platforms in terms of the positive predictive value (PPV).

We conclude that the active and pilot LSD screening programs in the United States are excellent, unbiased resources for those interested in initiating NBS for LSDs into their laboratories. Comparison of workflow, cost and performance metrics related to prospective newborn screening for multiple LSDs show significant cost and workflow advantages for DMF, but no clear performance advantage for either method.

Multiple sources of variability within the dried blood spot itself contribute to significant overlap of residual enzyme activities between true disease positives, pseudodeficiencies and certain carriers that lie within the cut-off range for several LSD enzymes, regardless of the screening method used. There is clearly an urgent need to improve the positive predictive value of these primary screening tests, the most promising of which are second-tier tests.