Heparan sulfate-derived terminal N-acetylglucosamine residues (Terminal GlcNAc-HS) (Terminal GlcNAc-HS)

Heparan sulfate-derived terminal N-acetylglucosamine (GlcNAc) residues are the specific carbohydrate moieties found at the non-reducing ends of partially degraded heparan sulfate chains within lysosomes. In normal physiological conditions, these residues are cleaved by the lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU) during the stepwise breakdown of glycosaminoglycans (Kan et al., 2014). A genetic deficiency in NAGLU leads to Mucopolysaccharidosis type IIIB (MPS IIIB), or Sanfilippo syndrome type B, characterized by the massive accumulation of these terminal GlcNAc residues in various tissues, particularly the brain (NORD, 2023). This accumulation is the primary driver of the severe, progressive neurodegeneration observed in affected children. Therapeutic strategies such as enzyme replacement therapy (ERT) with tralesinidase alfa (BMN 250) utilize a recombinant form of NAGLU to target and hydrolyze these residues, thereby reducing the lysosomal burden (BioMarin, 2021). Monitoring the reduction of these residues in the cerebrospinal fluid is a critical biomarker for evaluating the clinical efficacy of treatments aimed at halting disease progression (He et al., 2018).

Other names

Terminal alpha-N-acetylglucosamine residuesHeparan sulfate non-reducing end GlcNAcMPS IIIB storage materialHeparan sulfate-derived terminal N-acetylglucosamine residues in lysosomal glycosaminoglycan chains

Enzymatic hydrolysis of terminal alpha-N-acetylglucosamine residues by recombinant alpha-N-acetylglucosaminidase