Current developments in methodology to monitor the effect of treatment of lysosomal storage diseases (LSD): possibilities for newborn screening (NBS) in the Netherlands.

Abstract

A lysosome is an intracellular organelle that contains acid hydrolyses that degrades different kinds of macromolecules. Lysosomal storage diseases (LSD) are a group of more than 40 diseases, all caused by a deficiency of one or more enzymes. The absence or deficiency of the enzymes causes an accumulation of material within the lysosome. The clinical expression of LSD differs due to the different types of substrates that accumulate in the lysosome. This accumulation causes organ injury by affecting the metabolism of the cell. The clinical spectrum of LSD is very broad. There are different techniques to diagnose patients with a LSD, which are colorimetric assay based on DMB, thin layer chromatography, electrophoresis, enzyme tests and mass spectrometry. Therapeutic advances are hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, chemical chaperones and gene therapy. But only hematopoietic stem cell therapy and enzyme replacement therapy are in clinical use at present. A current development in methodology to monitor the effect of treatment and the activity of the LSD is tandem mass spectrometry. In most the countries LSD are not included in the NBS, except for a few states in the US where Pompe disease, Fabry, Gaucher and Krabbe are included. It is recommended to at least include the more relatively frequent LDS Pompe disease and MPS I, and secondly Gaucher disease and Krabbe disease in the NBS in the Netherlands.