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Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are negatively-charged polysaccharide compounds. They are composed of repeating disaccharide units that are present in every mammalian tissue.[1] Their functions within the body are widespread and determined by their molecular structure. Historically, the function of GAGs was thought to be limited to cell hydration and structural scaffolding. However, evidence now suggests that GAGs play a key role in cell signaling, which modulates a wide range of biochemical processes.[2] Some of these processes include regulation of cell growth and proliferation, promotion of cell adhesion, anticoagulation, and wound repair, among many more. The 4 primary groups of GAGs are classified based on their core disaccharide units and include heparin/heparan sulfate, chondroitin sulfate/dermatan sulfate, keratan sulfate, and hyaluronic acid.[3] This activity provides a summary of the molecular structures and resulting physiologic functions of the 4 primary groups of GAGs.

Pathophysiological processes related to GAGs are very broad due to their ubiquitous nature in the body. This section describes how GAGs are involved in the pathophysiology of various infectious processes, as well as in a group of rare genetic diseases known as Mucopolysaccharidoses (MPS), which are related to GAG metabolism. Infection GAGs are very important to the infectious processes of various viral, bacterial, fungal, and parasitic pathogens. The mechanisms by which these pathogens utilize GAGs to promote virulence vary based on the unique GAGs expressed in each organ system.[6] Pathogens that invade through the skin provide many examples of how GAGs are targeted to promote dermal infection. An intact skin epithelium is arguably the body’s most important defense against infection by providing a physical barrier composed of thick layers of dead keratinocytes. When this outer layer of skin is compromised, pathogens can invade and proliferate, causing infection, using GAGs. Merkel cell polyomavirus (MCV) is a double-stranded DNA virus that uses heparan sulfate and chondroitin sulfate on dermal cell surfaces to bind to and invade host cells, causing infection.[6] Group A Streptococci (GAS, Streptococcus pyogenes) are Gram-positive bacteria that represent another mechanism by which pathogens use GAGs to promote virulence. GAS utilizes a hyaluronic acid GAG-containing capsule to evade host immune defenses through molecular mimicry. Due to the abundance of hyaluronic acid already present in the dermis and epidermis, the hyaluronic acid capsule of GAS prevents recognition and subsequent phagocytosis by host leukocytes.[7] Examples of other pathogens that use GAGs to promote dermal infection include Herpes Simplex Virus (HSV), Candida, Staphylococcus Aureus, and Leishmania.[6] Mucopolysaccharidoses Mucopolysaccharidoses comprise a group of rare genetic diseases characterized by a deficiency of lysosomal enzymes required for the metabolism of GAGs.[8] This deficit results in lysosomal accumulation of GAG intermediates that eventually leads to cellular dysfunction and death. Mucopolysaccharidoses manifest with variable symptoms depending on the dysfunctional enzyme and the associated effects on GAG metabolism in organ systems.

Mucopolysaccharidoses comprise a group of rare genetic diseases characterized by a deficiency of lysosomal enzymes required for the metabolism of GAGs.[8] This deficit results in lysosomal accumulation of GAG intermediates that eventually leads to cellular dysfunction and death. Mucopolysaccharidoses manifest with variable symptoms depending on the dysfunctional enzyme and the associated effects on GAG metabolism in organ systems. Initial diagnostic steps of mucopolysaccharidoses following clinical suspicion include urinary GAG and enzyme assays. Confirmatory testing for mucopolysaccharidosis is via molecular diagnosis. Previously, treatment for mucopolysaccharidoses was based on symptom management. However, both enzyme replacement therapy and hematopoietic stem cell transplantation have been successfully used to treat certain subgroups of mucopolysaccharidosis.[9]