Keratan sulfate and chondroitin-6-sulfate (KS and C6S)

Keratan sulfate and chondroitin-6-sulfate are complex glycosaminoglycans (GAGs) that serve as essential structural components of the extracellular matrix, particularly within cartilage, bone, and the cornea [3,4]. These molecules are characterized by repeating disaccharide units with specific sulfation patterns that enable them to regulate tissue hydration, provide mechanical resistance to compression, and modulate cell signaling pathways [2]. In healthy individuals, these GAGs are continuously turned over in the lysosome; however, a deficiency in the enzyme N-acetylgalactosamine-6-sulfatase (GALNS) prevents their degradation [2]. This metabolic block leads to the systemic accumulation of keratan sulfate and chondroitin-6-sulfate, the hallmark of Mucopolysaccharidosis IV type A (Morquio A syndrome), which causes progressive skeletal dysplasia and respiratory issues [1,2]. Therapeutic intervention involves enzyme replacement therapy with elosulfase alfa, which acts directly on these accumulated substrates to restore catabolic activity [1]. By cleaving the 6-sulfate groups, the drug facilitates the clearance of these GAGs from the lysosomes, thereby slowing disease progression [1]. Monitoring urinary levels of these substrates serves as a key biomarker for assessing treatment efficacy [1]. References: [1] FDA. Vimizim (elosulfase alfa) Prescribing Information (2014). [2] StatPearls. Mucopolysaccharidosis Type IV (2023). [3] PubChem. Keratan sulfate (CID 24775). [4] PubChem. Chondroitin 6-sulfate (CID 24766).

Other names

Keratan sulphateChondroitin 6-sulphateGlycosaminoglycansGAGsKSC6S

Enzymatic hydrolysis of sulfate groups from the non-reducing terminal of the glycosaminoglycan chains by recombinant N-acetylgalactosamine-6-sulfatase (elosulfase alfa).