SGSH

The SGSH gene provides instructions for producing an enzyme called sulfamidase. This enzyme is located in lysosomes, compartments within cells that digest and recycle different types of molecules. Sulfamidase 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. Sulfamidase removes a sulfate molecule from a sugar called glucosamine when it is at the end of the GAG chain.

mucopolysaccharidosis type III - caused by mutations in the SGSH gene

More than 80 mutations in the SGSH gene have been found to cause mucopolysaccharidosis type IIIA (MPS IIIA). Most of these mutations change single DNA building blocks (nucleotides) in the gene. All of the mutations that cause MPS IIIA reduce or eliminate the function of sulfamidase.

The lack of sulfamidase activity disrupts the breakdown of a subset of GAGs called heparan sulfate. As a result, partially broken down heparan sulfate accumulates 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 IIIA.