Glycosaminoglycans (GAGs)

Accumulated glucuronate-containing glycosaminoglycans (GAGs) are the primary pathological substrates in several lysosomal storage disorders, most notably Mucopolysaccharidosis type VII (Sly syndrome) (NIH GARD, 2023). GAGs are long, unbranched polysaccharides consisting of repeating disaccharide units, including heparan sulfate, dermatan sulfate, and chondroitin sulfate, which are vital for extracellular matrix structure and cell signaling (Essentials of Glycobiology, 2017). In healthy cells, these molecules are systematically degraded by a series of lysosomal enzymes; however, genetic deficiencies in enzymes such as beta-glucuronidase result in their toxic accumulation within lysosomes (UniProt P08236). This progressive buildup leads to widespread cellular and tissue dysfunction, manifesting as skeletal deformities, hepatosplenomegaly, and cognitive impairment (StatPearls, 2023). Therapeutic interventions like enzyme replacement therapy (ERT), including drugs such as vestronidase alfa, aim to provide functional recombinant enzymes that catalyze the breakdown of these accumulated GAGs (DrugBank DB13873). By facilitating the clearance of these substrates, these treatments help reduce lysosomal volume and mitigate the multi-systemic symptoms associated with the disease. Monitoring of urinary GAG levels is frequently used as a biomarker to assess the efficacy of these therapeutic interventions in clinical practice.

Other names

MucopolysaccharidesAcid mucopolysaccharidesLysosomal GAGs

Enzymatic degradation of accumulated glycosaminoglycans via exogenous lysosomal hydrolases (Enzyme Replacement Therapy).