The ARSB gene provides instructions for producing an enzyme called arylsulfatase B, which is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). Specifically, arylsulfatase B removes a chemical group known as a sulfate from two GAGs called dermatan sulfate and chondroitin sulfate. Arylsulfatase B is located in lysosomes, compartments within cells that digest and recycle different types of molecules.
More than 130 mutations in the ARSB gene have been found to cause mucopolysaccharidosis type VI (MPS VI). Most of these mutations change single DNA building blocks (nucleotides) in the gene. All of the mutations that cause MPS VI reduce or eliminate the function of arylsulfatase B. It usually cannot be determined whether a certain mutation will cause severe or mild MPS VI; however, mutations known to result in the complete absence of arylsulfatase B activity cause severe signs and symptoms.
The lack of arylsulfatase B activity leads to the accumulation of GAGs within lysosomes. Conditions such as MPS VI that cause molecules to build up inside the lysosomes are called lysosomal storage disorders. The accumulation of GAGs within lysosomes increases the size of cells, which is why many tissues and organs are enlarged in this disorder. Researchers believe that the buildup of GAGs may also interfere with the functions of other proteins inside lysosomes, triggering inflammation and cell death.
- arylsulfatase B isoform 1 precursor
- N-acetylgalactosamine 4-sulfate sulfohydrolase