Lysosomal Storage Disorders

Lysosomal storage diseases are a group of disorders, each characterized by a specific lysosomal enzyme deficiency in a variety of tissues. This leads to an intracellular accumulation of a variety of undegraded cellular substrates, including, sphigolipids, glycosaminoglycan and glycogen. Forty lysosomal storage diseases are presently known. As a group they occur with an estimated frequency of 1:5000 to 1:8000, but each of them is rare. LSDs display considerable clinical and biochemical heterogeneity. In most cases these disorders are characterized by a progressive, highly debilitating or lethal course, causing severe handicap in patients resulting in significant social burden. Furthermore, many of these diseases affect children in the first decade of life. The characterization of the specific metabolites and genetic defects at the basis of LSD have markedly increased our understanding of lysosomal biology, including enzyme targeting, intracellular transport and structure and function of the enzymes and cofactors involved in the degradation of complex macromolecules.

The four specific LSDs (Gaucher disease, Pompe disease, Mucopolysaccharidosis VI, Multiple Sulfatase Deficiency) that will be studied by the EUCLYD consortium have unique characteristics. Pompe disease, Gaucher disease and MPS VI are caused by single enzyme deficiencies, due to mutations in genes encoding lysosomal hydrolases, as observed in most lysosomal disorders. MSD is a unique lysosomal disease, in which the molecular defect is at a post-translational modification of all members of the sulfatase family; this leads to the simultaneous deficiency of all sulfatases (either lysosomal or non-lysosomal), thus resulting in a peculiar model of disease in which the activity of an entire family of proteins is inactive.
All four diseases also differ for the type of stored material. Gaucher disease is the most frequent sphingolipidosis, MPS VI is characterized by the storage of glycosaminoglycans, MSD by mixed storage and Pompe disease is unique as is the only lysosomal disease characterized by intralysosomal storage of glycogen. The wide range of stored substrates is of interest since it may shed light on the different secondary mechanisms involved in cell and tissue damage.
Finally, the diseases studied are characterized by involvement of different tissues with the exclusion of CNS involvement (apart from MSD as a very peculiar model): histiocytes/macrophages in Gaucher disease with visceral and bone disease, muscle in Pompe disease, visceral, bone-joints and heart generalized in MPS and MSD.

Read more at:
The Merck Manuals Online Medical Library

Patient organizations:
Association for Glycogen Storage Disease
Association for Glycogen Storage Disease (UK)
Associazione Italiana Glicogenosi
Vaincre les Maladies Lysosomales
Association Francophone des Glycogenoses
Selbsthilfegruppe Glykogenose Deutschland e.V.