Alpha-L-iduronic acid residues in dermatan sulfate and heparan sulfate (IDUA substrates)

Alpha-L-iduronic acid residues are the terminal carbohydrate components of the glycosaminoglycans (GAGs) dermatan sulfate and heparan sulfate, which are essential structural and functional elements of the extracellular matrix (UniProt P35475). Under normal physiological conditions, these residues are cleaved by the lysosomal enzyme alpha-L-iduronidase (IDUA) as part of the stepwise degradation of GAGs (StatPearls, Mucopolysaccharidosis Type I). In patients with Mucopolysaccharidosis type I (MPS I), a genetic deficiency in IDUA leads to the pathological accumulation of these partially degraded GAGs within lysosomes across nearly all organ systems (NIH GARD, MPS I). This accumulation results in a spectrum of clinical manifestations, including skeletal abnormalities, organomegaly, cardiovascular complications, and, in severe cases, progressive neurodegeneration (PubMed, PMID: 25107314). Therapeutic intervention primarily involves enzyme replacement therapy (ERT) with laronidase, a recombinant form of human IDUA, which targets these accumulated substrates to facilitate their breakdown and clearance (PubChem, CID: 16131100). Monitoring the levels of these specific GAG residues in urine and blood is the standard method for diagnosing the disease and assessing the efficacy of therapeutic interventions.

Other names

Dermatan sulfateHeparan sulfateGlycosaminoglycansMucopolysaccharidesGAGsAlpha-L-iduronic acid-containing glycosaminoglycans

Hydrolytic cleavage of terminal alpha-L-iduronic acid residues from dermatan sulfate and heparan sulfate by exogenous recombinant human alpha-L-iduronidase.