Alpha-L-iduronidase (IDUA) (IDUA)

Alpha-L-iduronidase (IDUA) is a vital lysosomal enzyme responsible for the stepwise degradation of glycosaminoglycans (GAGs), specifically dermatan sulfate and heparan sulfate (UniProt P35475). It functions by hydrolyzing the terminal alpha-L-iduronic acid residues from these complex polysaccharides. A deficiency in IDUA activity, typically caused by autosomal recessive mutations in the IDUA gene, leads to Mucopolysaccharidosis type I (MPS I), a progressive lysosomal storage disorder (NCBI Gene ID: 3425). The resulting accumulation of GAGs within lysosomes causes widespread cellular and tissue dysfunction, manifesting as skeletal abnormalities, organomegaly, and in severe cases, significant neurodegeneration. The primary therapeutic approach is enzyme replacement therapy (ERT) with laronidase (Aldurazyme), a recombinant human IDUA that facilitates the breakdown of stored GAGs (FDA Label: Aldurazyme). While ERT is effective for systemic symptoms, its inability to cross the blood-brain barrier remains a significant challenge for treating the central nervous system manifestations of the disease.

Other names

IDUAL-iduronidaseAlpha-L-iduronide iduronohydrolaseHurler syndrome protein

Enzyme replacement therapy (ERT) providing exogenous enzyme to restore catalytic activity for the degradation of accumulated glycosaminoglycans.