The most common LSDs are diagnosed by measuring the activity of the lysosomal enzyme. The malfunctioning of this enzyme leads to the accumulation of its substrate within the lysosomes. Such lysosomal enzymes are e.g. acid-β-glucocerebrosidase (ABG), acid-sphingomyelinase (ASM), acid‑α‑glucosidase (GAA), β‑galactocerebrosidase (GALC), α-galactosidase A (GLA) and α-L-iduronidase (IDUA) where their activities may aid in the diagnosis of Gaucher Disease, Niemann-Pick A/B Disease, Pompe Disease, Krabbe Disease, Fabry Disease, and MPS I Disease, respectively.
Enzyme acitivities can be measured from dried blood spots (DBS) using tandem mass spectrometry or fluorescence based assays. Tandem mass spectrometry-based assays allow simultaneous detection of multiple enzymes’ activities whereas fluorescence-based assays are used to measure individual enzyme’s activities.