Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is a rare autosomal recessive lysosomal storage disease that primarily affects the brain and spinal cord. It is caused by a buildup of large sugar molecules called glycosaminoglycans (AKA GAGs, or mucopolysaccharides) in the body's lysosomes. Affected children generally do not show any signs or symptoms at birth, although some early indicators can be respiratory issues at birth, large head size, and umbilical hernia. In early childhood, they begin to develop developmental disability and loss of previously learned skills. In later stages of the disorder, they may develop seizures and movement disorders. Patients with Sanfilippo syndrome usually live into adolescence or early adulthood. Signs and symptoms The disease manifests in young children. Symptoms usually begin to appear between two and six years of age. Affected infants appear normal, although some mild facial dysmorphism may be noticeable. Of all of the MPS diseases, Sanfilippo syndrome produces the fewest physical abnormalities. After an initial symptom-free interval, patients usually present with a slowing of development and/or behavioral problems, followed by progressive intellectual decline resulting in severe dementia and progressive motor disease. Acquisition of speech is often slow and incomplete. The disease progresses to increasing behavioral disturbance including temper tantrums, hyperactivity, destructiveness, aggressive behavior, pica, difficulties with toilet training, and sleep disturbance. As affected children initially have normal muscle strength and mobility, the behavioral disturbances may be difficult to manage. Disordered sleep in particular presents a significant problem to care providers. In the final phase of the illness, children become increasingly immobile and unresponsive, often require wheelchairs, and develop swallowing difficulties and seizures. The life-span of an affected child does not usually extend beyond late teens to early twenties. Individuals with MPS type III tend to have mild skeletal abnormalities; osteonecrosis of the femoral head may be present in severe cases. Optic nerve atrophy, deafness, and otitis can be seen in moderate to severe cases. Other characteristics include coarse facial features, thick lips, synophrys, and stiff joints. It is difficult to clinically distinguish differences among the four types of Sanfilippo syndrome. However, type A is usually the most severe subtype, characterized by earliest onset, rapid clinical progression with severe symptoms, and short survival. The median age of death for children afflicted with type A is 15.4 ± 4.1 years. It is important that simple and treatable conditions such as ear infections and toothaches not