Sanfilippo syndrome is caused by mutations that lead to the body being unable to break down a complex sugar molecule called heparan sulfate. There are four types of Sanfilippo syndrome, each the result of a mutation in a different gene. Types A and B are more common, while types C and D are rarer.
Each of the four genes implicated in Sanfilippo is important for the step-by-step process by which cells break down heparan sulfate. As such, in all four types, heparan sulfate builds up inside cells. Therefore, all four types have very similar symptoms, even though the faulty gene is different in each type.
Mutations in the SGSH gene cause Sanfilippo syndrome type A. This gene contains the instructions necessary for cells to make the N-sulphoglucosamine sulphohydrolase enzyme. This enzyme is responsible for removing a chemical group called sulfate from the end of a particular type of sugar molecule.
Type B is caused by mutations in the NAGLU gene, which encodes for the enzyme alpha-N-acetylglucosaminidase. This enzyme is responsible for removing a type of chemical group called alpha-N-acetylglucosamine from heparan sulfate.
Mutations in the HGSNAT gene cause type C. This gene encodes for the heparan-alpha-glucosaminide N-acetyltransferase enzyme, which is responsible for adding a chemical group, called an acetyl group, to the end of the heparan sulfate molecule. The addition of the acetyl group is necessary for the subsequent activity of the alpha-N-acetylglucosaminidase enzyme.
People with this type of disease generally live longer than those with types A or B.
Type D is the rarest form of Sanfilippo. Mutations in the GNS gene cause this type. GNS encodes for the N-acetylglucosamine-6-sulfatase enzyme, which is responsible for removing sulfate groups from the end of certain sugar molecules (though notably, different molecules than those affected by the N-sulphoglucosamine sulphohydrolase enzyme).