Diseases of GAG catabolism

Diseases of GAG chains are not limited to their biosynthetic defects, but also encompass catabolic defects, which result in the accumulation of non-degraded GAG fragments in lysosomes. These lysosomal storage diseases are also known as mucopolysaccharidoses, which are subdivided into different clinical entities. For example, Hurler disease, which is caused by defective a-iduronase activity, is characterized by features like dwarfism, psychomotor retardation and facial dysmorphy. The a-iduronase deficiency impaired the degradation of heparan sulfate and dermatan sulfate chains. Some types of mucopolysaccharidosis consist of several genetic disorders. Along this way, Sanfilippo disease includes four distinct enzymatic defects of heparan sulfate degradation. Clinically, Sanfilippo disease is associated with severe psychomotor retardation without other organ dysfunctions. Mucopolysaccharidoses are rare inherited diseases with an incidence below 1:30’000. Other forms of lysosomal storage diseases are related to the catabolism of glycosphingolipids (see the corresponding chapter).

FIG: MUCOPOLYSACCHARIDOSES TABLE