Lysosomal storage disorders (LSD) represent a group of over 40 metabolic diseases caused by deficient enzymes specializing in catabolic degradation of lipids, saccharides, proteins and their conjugates such as glycolipids and lipoproteins. LSD are rare disorders that do not present in affected children at birth and are difficult to diagnose before organ or systemic damage sets in. In the last decade, sophisticated treatments based on enzyme replacement or erythropoietic stem cell transplantation therapies have been developed for several LSD that stressed the need for an early detection of affected newborns by large scale screening. We have been developing diagnostic methods based on affinity-capture release mass spectrometry and tandem mass spectrometry (MS/MS). The MS/MS methods are suitable for large-scale newborn screening of entire newborn populations, e.g., &gt;1,500,000 newborns in New York state and &gt;120,000 newborns in Washington state. The lecture will describe the new generation chemistry of assays for enzymes responsible for deficient sphingolipid degradation, mucopolysaccharidoses, and neuronal ceroid lipofuscinoses. These assays have been tailored for bioanalytical work with dried blood spots to be compatible with the workflow in state newborn screening centers. The new MS/MS methods show better performance than fluorescence-based methods in that they allow massive multiplexing of quantitative analyses of several enzymes by tandem mass spectrometry and achieve higher dynamic range. The MS/MS methods have been licensed for commercial development and use.

New approaches to multiplex newborn screening of lysosomal storage disorders by tandem mass spectrometry

249th National Meeting (2015)

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