Here, we present results from a proof-of-principle study, evaluating an innovative digital microfluidics (DMF) platform, referred to as SEEKER®, that can measure the activity of the following four lysosomal enzymes from DBS: α-L-iduronidase (IDUA) for mucopolysaccharidosis I (MPS I), acid α-glucosidase (GAA) for Pompe disease, β-glucosidase (GBA) for Gaucher disease, and α-galactosidase A (GLA) for Fabry disease. This evidence concerns the gene GLA and Scheie syndrome.