GNS

The GNS gene provides instructions for producing an enzyme called N-acetylglucosamine-6-sulfatase. This enzyme is located in lysosomes, compartments within cells that digest and recycle different types of molecules. N-acetylglucosamine-6-sulfatase is involved in the step-wise breakdown of large molecules called glycosaminoglycans (GAGs). GAGs are composed of sugar molecules that are linked together to form a long string. To break down these large molecules, individual sugars are removed one at a time from one end of the molecule. N-acetylglucosamine-6-sulfatase removes a sulfate molecule from a subset of GAGs called heparan sulfate when the sugar N-acetylglucosamine-6-sulfate is located at the end.

mucopolysaccharidosis type III - caused by mutations in the GNS gene

Mutations in the GNS gene cause mucopolysaccharidosis type IIID (MPS IIID). Most of these mutations change single DNA building blocks (nucleotides) in the gene. All of the mutations that cause MPS IIID reduce or eliminate the function of N-acetylglucosamine-6-sulfatase.

The lack of N-acetylglucosamine-6-sulfatase activity disrupts the breakdown of heparan sulfate. As a result, partially broken down GAGs accumulate within lysosomes. Researchers believe that the accumulation of GAGs interferes with the functions of other proteins inside the lysosomes and disrupts the normal functions of cells. It is unknown why the buildup of heparan sulfate mostly affects the central nervous system in MPS IIID.