Abstract
Mucolipidosis II and III (ML II/III) are caused by a deficiency of uridine-diphosphate N-acetylglucosamine: lysosomal-enzyme-N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase, EC2.7.8.17), which tags lysosomal enzymes with a mannose 6-phosphate (M6P) marker for transport to the lysosome. The process is performed by a sequential two-step process: first, GlcNAc-1-phosphotransferase catalyzes the transfer of GlcNAc-1-phosphate to the selected mannose residues on lysosomal enzymes in the cis-Golgi network. The second step removes GlcNAc from lysosomal enzymes by N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase (uncovering enzyme) and exposes the mannose 6-phosphate (M6P) residues in the trans-Golgi network, in which the enzymes are targeted to the lysosomes by M6Preceptors. A deficiency of GlcNAc-1-phosphotransferase causes the hypersecretion of lysosomal enzymes out of cells, resulting in a shortage of multiple lysosomal enzymes within lysosomes. Due to a lack of GlcNAc-1-phosphotransferase, the accumulation of cholesterol, phospholipids, glycosaminoglycans (GAGs), and other undegraded substrates occurs in the lysosomes. Clinically, ML II and ML III exhibit quite similar manifestations to mucopolysaccharidoses (MPSs), including specific skeletal deformities known as dysostosis multiplex and gingival hyperplasia. The life expectancy is less than 10 years in the severe type, and there is no definitive treatment for this disease. In this review, we have described the updated diagnosis and therapy on ML II/III.
Highlights
Mucolipidoses (MLs) are classified as a lysosomal storage diseases (LSDs) because of their involvement in increased storage materials in the lysosomes
It is important to note that ML II and ML III cannot be distinguished from each other based on lysosomal enzyme activities or mannose 6-phosphate (M6P)-containing proteins
This mouse lacks cartilage defects and retinal degeneration, grows normally, and shows a normal life span, predominant lesions are found in the secretory epithelial cells of exocrine glands similar to those seen in the first Gnptab gene trap mice [101]
Summary
Mucolipidoses (MLs) are classified as a lysosomal storage diseases (LSDs) because of their involvement in increased storage materials in the lysosomes. Patients with MLs are born with a genetic defect in which their bodies either do not produce enough enzymes or, in some instances, produce ineffective forms of enzymes, resulting in the accumulation of storage materials in the cells of various tissues in the body and successive damage of organs [2]. In patients with MLs, the molecules accumulate in the brain, visceral organs, and muscle tissue as well as in the bone, causing mental retardation, skeletal deformities, and poor function of vital organs such as the liver, spleen, heart, and lungs. Sialidosis is caused by the deficiency of alpha-N-acetyl neuraminidase due to mutations in the neuraminidase 1 gene (NEU1) resulting in the. Odification of the N-linked carbohydrate chain on lysosomal hydrolases. The site-1 protease cleaves inactive precursor protein and releases catalytically active α and β subunits
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