Congenital Disorders Caused by Defects in Catabolism of Glycosaminoglycans

Abstract

Glycosaminoglycans (GAGs), including chondroitin sulfate, dermatan sulfate, heparan sulfate, and hyaluronan, are ubiquitously present on animal cell surfaces as well as in the extracellular matrix, and they are involved in various biological events, such as cell adhesion, regulation of cell signaling, and construction of extracellular matrix. Most GAGs are internalized into cells by endocytosis and depolymerized into monosaccharides by endo- and exo-type enzymes of endosomes and lysosomes. A part of GAGs is also degraded extracellularly, which may be involved in the regulation of their functions. Mucopolysaccharidoses are caused by a deficiency of exo-type GAG-degrading enzymes. Although some hereditary diseases are considered to be involved in mutations in the genes coding endo-type GAG-degrading enzymes, the physiological mechanisms remain to be clarified. The frequency of mucopolysaccharidoses is higher than that of other GAG-related genetic diseases. Since mucopolysaccharidoses have been investigated for a long time, the methods to treat them have been established to some extent. However, there are several problems to be overcome to realize effective treatments. In this review, hereditary diseases caused by abnormality of GAG-catabolism are outlined from the standpoint of glycobiology.