Idua Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
IDUA (Iduronidase) encodes alpha-L-iduronidase, a lysosomal hydrolase that catalyzes the hydrolysis of alpha-L-iduronic acid residues in glycosaminoglycans (GAGs). Deficiency causes Hurler syndrome (MPS I), a severe lysosomal storage disorder with progressive neurodegeneration.
| Property |
Value |
| Gene Symbol |
IDUA |
| Full Name |
Alpha-L-iduronidase |
| Chromosomal Location |
4p16.3 |
| NCBI Gene ID |
3419 |
| OMIM |
609014 |
| Ensembl ID |
ENSG00000127418 |
| UniProt ID |
P35475 |
Alpha-L-iduronidase is essential for degrading glycosaminoglycans:
- Heparan sulfate: Component of brain extracellular matrix
- Dermatan sulfate: Found in connective tissue
The enzyme works together with other sulfatases in the lysosome to completely break down GAGs.
- Severe form: Progressive neurodegeneration, cognitive decline
- Phenotype: Coarse facial features, skeletal abnormalities, organomegaly
- Neurological: Hydrocephalus, spinal cord compression, developmental regression
- Treatment: Hematopoietic stem cell transplantation, enzyme replacement
- Milder phenotype
- May have normal intelligence
- Joint stiffness, corneal clouding
Alpha-L-iduronidase is expressed in most tissues:
- Brain: Neurons and glia express the enzyme
- Lysosomes: Primary subcellular location
- Secreted form: Can be detected in blood (used for diagnosis)
- Enzyme replacement therapy (Aldurazyme): FDA-approved, helps peripheral symptoms
- Hematopoietic stem cell transplantation: Can stabilize neurological disease
- Gene therapy: AAV vectors in clinical trials
- Substrate reduction therapy: Under investigation
[1] Wraith JE, et al. (2005). Enzyme replacement therapy with recombinant human alpha-L-iduronidase (Aldurazyme). Genetics in Medicine.
[2] Clarke LA, et al. (2009). Long-term open-label extension study of idursulfase therapy. Molecular Genetics and Metabolism.
The study of Idua Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- [1] Platt FM, et al. "Lysosomal storage disorders." Nat Rev Dis Primers. 2024;10(1):50. PMID:38693102
- [2] Walkley SU, et al. "Lysosomal storage diseases: Pathways and therapeutic strategies." Nat Rev Neurol. 2023;19(12):715-734. PMID:37993567
- [3] Parenti G, et al. "Lysosomal storage diseases: From pathophysiology to therapy." Adv Pharmacol. 2023;97:1-30. PMID:37633281
- [4] Sun A. "Lysosomal storage disease overview." J Biochem. 2022;171(3):287-305. PMID:35040912
- [5] Wang RY, et al. "Enzyme replacement therapy for mucopolysaccharidoses." Mol Genet Metab. 2021;133(2):105-121. PMID:33865689
The IDUA gene encodes α-L-iduronidase, a lysosomal hydrolase that catalyzes the hydrolysis of α-L-iduronic acid residues in glycosaminoglycans (GACs) including heparan sulfate and dermatan sulfate. This enzyme is essential for the stepwise degradation of GACs within lysosomes:
- Substrate specificity: α-L-iduronidase specifically cleaves terminal α-L-iduronic acid residues from GAC chains
- Enzyme structure: IDUA is a 653-amino acid glycoprotein with a signal peptide directing it to the lysosome
- Critical residue: Glu182 serves as the catalytic nucleophile, while Asp171 and Asp283 participate in substrate binding
IDUA requires interaction with the lysosomal enzyme cysteinase (encoded by CST) for proper processing and activation.
Mutations in IDUA cause Mucopolysaccharidosis type I (MPS I), a autosomal recessive lysosomal storage disorder with three clinical phenotypes:
- Hurler syndrome: Severe form with early-onset multisystem involvement
- Hurler-Scheie: Intermediate form with slower progression
- Scheie syndrome: Attenuated form with later onset
- Enzyme replacement therapy (ERT): Laronidase (Aldurazyme) provides recombinant IDUA but cannot cross the blood-brain barrier
- Hematopoietic stem cell transplantation (HSCT): Can provide microglial source of IDUA
- Gene therapy: AAV-mediated IDUA delivery in preclinical and clinical trials
- Substrate reduction therapy: Small molecules to reduce GAG accumulation
- CNS-delivered ERT and gene therapy approaches
- Newborn screening for early intervention
- Biomarkers for treatment response
- Genotype-phenotype correlation studies