Congenital Disorders Caused by Defects in Anabolism of Glycosaminoglycans

Abstract

Glycosaminoglycans (GAGs), including chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin, and hyaluronan, are important for various biological processes including construction of the extracellular matrix, tissue development, and cell signaling through interaction with extracellular matrix components, morphogens, and growth factors. GAGs are synthesized by various glycosyltransferases and sulfotransferases using donor substrates including uridine diphosphate (UDP)-sugars and 3′-phosphoadenosine 5′-phosphosulfate, respectively. GAGs as well as UDP and adenosine-3′, 5′-bisphosphate, which are reaction products, are mainly catabolized in lysosomes and the Golgi apparatus. Disturbances in the anabolism and catabolism of GAGs cause human genetic diseases such as connective tissue disorders and mucopolysaccharidoses, respectively. Furthermore, disturbances of catabolism of UDP and adenosine-3′, 5′-bisphosphate also cause Desbuquois dysplasia type 1 and chondrodysplasia with joint dislocations, respectively. Effective therapy for genetic disorders caused by defects in the biosynthesis of GAGs has not been established. This review provides an overview of the growing number of glycobiological studies on characterized genetic disorders caused by faults in the anabolism of GAGs.