Tandem mass spectrometry in the detection of inborn errors of metabolism for newborn screening

Abstract

Tandem mass spectrometry has been used for determinations of enzyme activities in biological samples. Activities in rehydrated dried blood spots of lysosomal enzymes glucocerebrosidase, acid sphingomyelinase, galactocerebroside beta-galactosidase, acid-alpha-galactosidase, acid alpha-glucosidase, and alpha-D-iduronidase are measured simultaneously by multiple-reaction monitoring of ion dissociations from cations produced by electrospray ionization of enzymatic products. Simple and inexpensive assay protocols are described that are readily adopted for handling multiple samples in 96-well microtiter plates, employing simple separation steps, and using less than or equal to 3 micromol of synthetic or commercially available substrates, and less than 25 nmol of internal standards per analysis. The assays have the potential of being used for large-scale screening of newborns for the detection of inborn errors of metabolism.