MPS III, also known as Sanfilippo Syndrome, is a lysosomal storage disorder, caused by deficiency in activity of one of the lysosomal enzymes needed to degrade heparin sulfate. The disorder is especially harmful to the central nervous system, and also affects the skeletal system. CNS manifestations of the disease result in progressive dementia, mental retardation, hyperactivity, seizures, aggressiveness, as well as loss of hearing and vision. Skeletal involvement is exemplified by joint abnormalities which restrict movement. Other features of the condition include chronic colds, thickened skin, facial dysmorphism, hirsutism, and ear infections. Normally, the disease progresses through three distinct stages; the first stage beginning around the age of 2-years, and the third stage lasting till about 10-years of age. Four different forms of MPSIII are known, based on the enzyme that is defective. Sanfilippo A or MPS IIIA is the most severe of these forms, and has the shortest survival rate among all the MPS III disorders.

The genetic defect in MPS IIIA involves the SGSH gene on the long arm of chromosome 17. N-sulfoglycosamine sulfohydrolase, encoded for by this gene catalyzes the third step in the degradation of mucopolysaccharides. Mutations in this gene result in accumulation of mucopolysaccharides and their metabolites in the lysosomes, causing cell, tissue, and organ dysfunction.