Newborn screening for the full set of mucopolysaccharidoses in dried blood spots based on first-tier enzymatic assay followed by second-tier analysis of glycosaminoglycans

Newborn screening (NBS) for the full set of mucopolysaccharidoses (MPSs) is now possible by either measuring all of the relevant enzymatic activities in dried blood spots (DBS) using tandem mass spectrometry followed by measurement of accumulated glycosaminoglycans (GAGs) or the vice-versa approach. In this study we considered multiple factors in detail including reagent costs, time per analysis, false positive rates, instrumentation requirements, and multiplexing capability. Both NBS approaches are found to provide acceptable solutions for comprehensive MPS NBS, but the enzyme-first approach allows for better multiplexing to include numerous additional diseases that are appropriate for NBS expansion. By using a two-tier NBS approach, the false positive and false negatives rates are expected to acceptably low and close to zero.

Automated summary

Newborn screening for mucopolysaccharidoses can be done by measuring enzymatic activities or accumulated substances in dried blood spots. Both approaches provide acceptable solutions for screening, but the enzyme-first approach allows for better multiplexing.