Abstract
Mucopolysaccharidoses (MPS) belong to the group of lysosomal storage diseases and
are characterized by the deficiency of lysosomal enzymes involved in the degradation
of glycosaminoglycans (GAGs). They are caused by inherited enzyme deficiencies that
result from mutated genes producing defective enzymes. In MPS, the step-wise degradation
process of GAG chains is impaired, and thus pieces of undegraded chains remain in
the lysosomes impeding other processes in these cell organelles. Several enzymes—currently
12 are known—are necessary to degrade GAGs to sugars and small chemical substances,
such as sulfate- or amino groups, to prepare them for excretion via exocytosis or
to reintegrate them into new molecules by recycling. GAGs are major components of
the connective tissue but play a role in shaping the vicinity of each cell surface
as well; hence, any disturbance in their metabolism causes problems not limited to
connective tissue but other tissues and organs. Therefore, MPS are multisystemic diseases
involving many organs and restrict a wide range of organ functions. Organomegaly,
typical skeletal changes known as “dysostosis multiplex,” excessive storage in the
nervous system with neurologic symptoms and impaired cognitive function have been
known as the typical symptoms of the first classical MPS types for some time now.
Because of new therapies and improved care, the life expectancy of MPS patients has
increased significantly. Results of investigations that have only become available
recently and new methods allowing for fine-meshed observation have revealed unexpected
findings. These outcomes are not limited to excessive storage: patients show unpredictable
reactions of the immune system, chronic inflammation, changes in metabolic pathways
not directly related to the connective tissue, such as chronic arthritis, osteopenia,
Parkinson-like symptoms, signs of dementia, and many more, which suggest that lysosomes
have many more roles than just degradation of no longer needed macromolecules.
Keywords
mucopolysaccharide storage disease - lysosome - endosomes - inflammation - autophagy
