L-iduronidase
L-iduronidase is an enzyme that plays a critical role in the breakdown of glycosaminoglycans (GAGs), specifically heparan sulfate and dermatan sulfate. These complex sugars are found in the extracellular matrix and on cell surfaces. L-iduronidase is necessary for the lysosomal degradation of these molecules, which is essential for cellular function and development.
Function[edit | edit source]
L-iduronidase hydrolyzes the non-reducing terminal iduronic acid residues in glycosaminoglycans, converting them into anhydrotalitol. This enzymatic activity is crucial for the stepwise degradation of GAGs within the lysosome, a specialized organelle responsible for breaking down cellular waste and recycling materials. Without proper function of L-iduronidase, GAGs accumulate in the lysosomes, leading to cellular dysfunction and disease.
Genetic and Molecular Basis[edit | edit source]
The gene responsible for encoding L-iduronidase is located on the human chromosome 4p16.3. Mutations in this gene can lead to deficient or dysfunctional enzyme production, resulting in a spectrum of disorders known as mucopolysaccharidoses (MPS), specifically Mucopolysaccharidosis type I (MPS I). MPS I is divided into three subtypes based on severity: Hurler syndrome (MPS IH), Hurler-Scheie syndrome (MPS IH/S), and Scheie syndrome (MPS IS), with Hurler syndrome being the most severe.
Clinical Significance[edit | edit source]
The deficiency of L-iduronidase activity leads to the accumulation of GAGs in various tissues and organs, causing the symptoms associated with MPS I. These can include developmental delay, organ dysfunction, skeletal abnormalities, and, in severe cases, early death. Diagnosis of MPS I typically involves measuring the activity of L-iduronidase in leukocytes or fibroblasts, followed by genetic testing to identify specific mutations in the gene.
Treatment[edit | edit source]
Treatment options for MPS I have expanded over the years and now include enzyme replacement therapy (ERT) with synthetic L-iduronidase, known as laronidase (Aldurazyme®). ERT has been shown to improve many of the physical symptoms of MPS I, although it has limited ability to treat neurological manifestations due to its inability to cross the blood-brain barrier. Hematopoietic stem cell transplantation (HSCT) is another treatment option, particularly effective in younger patients with severe MPS I, as it can also address the neurological aspects of the disease.
Research Directions[edit | edit source]
Research into L-iduronidase and MPS I continues to focus on improving treatment outcomes and understanding the molecular mechanisms underlying the disease. Gene therapy, aimed at delivering a functional copy of the gene to affected individuals, represents a promising area of research. Additionally, strategies to enhance the delivery of ERT to the brain or to develop more effective enzyme formulations are under investigation.
Search WikiMD
Ad.Tired of being Overweight? Try W8MD's physician weight loss program.
Semaglutide (Ozempic / Wegovy and Tirzepatide (Mounjaro / Zepbound) available.
Advertise on WikiMD
WikiMD's Wellness Encyclopedia |
Let Food Be Thy Medicine Medicine Thy Food - Hippocrates |
Translate this page: - East Asian
中文,
日本,
한국어,
South Asian
हिन्दी,
தமிழ்,
తెలుగు,
Urdu,
ಕನ್ನಡ,
Southeast Asian
Indonesian,
Vietnamese,
Thai,
မြန်မာဘာသာ,
বাংলা
European
español,
Deutsch,
français,
Greek,
português do Brasil,
polski,
română,
русский,
Nederlands,
norsk,
svenska,
suomi,
Italian
Middle Eastern & African
عربى,
Turkish,
Persian,
Hebrew,
Afrikaans,
isiZulu,
Kiswahili,
Other
Bulgarian,
Hungarian,
Czech,
Swedish,
മലയാളം,
मराठी,
ਪੰਜਾਬੀ,
ગુજરાતી,
Portuguese,
Ukrainian
Medical Disclaimer: WikiMD is not a substitute for professional medical advice. The information on WikiMD is provided as an information resource only, may be incorrect, outdated or misleading, and is not to be used or relied on for any diagnostic or treatment purposes. Please consult your health care provider before making any healthcare decisions or for guidance about a specific medical condition. WikiMD expressly disclaims responsibility, and shall have no liability, for any damages, loss, injury, or liability whatsoever suffered as a result of your reliance on the information contained in this site. By visiting this site you agree to the foregoing terms and conditions, which may from time to time be changed or supplemented by WikiMD. If you do not agree to the foregoing terms and conditions, you should not enter or use this site. See full disclaimer.
Credits:Most images are courtesy of Wikimedia commons, and templates Wikipedia, licensed under CC BY SA or similar.
Contributors: Prab R. Tumpati, MD