D-galactose 6-sulfate residues in keratan sulfate (Gal6S)

D-galactose 6-sulfate (Gal6S) is a specific sulfated monosaccharide residue that constitutes a key part of the repeating disaccharide units in keratan sulfate (KS), a glycosaminoglycan (GAG) essential for the structural integrity of the cornea, cartilage, and bone (nih.gov). In normal physiological conditions, the lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS) is responsible for the hydrolytic removal of the sulfate group at the C-6 position of Gal6S, allowing for the proper catabolism of KS (ucsc.edu). A deficiency in this enzyme leads to Mucopolysaccharidosis type IVA (MPS IVA), or Morquio A syndrome, a lysosomal storage disorder characterized by the systemic accumulation of undegraded KS and chondroitin-6-sulfate (nih.gov). This accumulation causes progressive and severe skeletal dysplasia, joint abnormalities, and impaired mobility (clinicaltrialsarena.com). The degree of sulfation on these residues influences the physical properties of the keratan sulfate chains, such as their hydration and interaction with other matrix proteins (nih.gov). Elosulfase alfa (Vimizim) is an enzyme replacement therapy that acts directly on these Gal6S residues to restore degradative capacity, thereby reducing the lysosomal storage burden and improving the physical endurance of affected patients (drugs.com). Monitoring of Gal6S-containing disaccharides in urine and plasma serves as a critical biomarker for assessing disease severity and therapeutic efficacy (nih.gov).

Other names

Galactose-6-sulfate6-O-sulfo-D-galactoseKeratan sulfate galactose 6-sulfateGal6S

Elosulfase alfa, a recombinant form of the human lysosomal enzyme N-acetylgalactosamine-6-sulfatase (GALNS), provides the enzymatic activity required to hydrolyze the 6-sulfate groups from D-galactose 6-sulfate residues in keratan sulfate, facilitating its degradation and clearance from lysosomes.