Sanfilippo syndrome differs from other forms of mucopolysaccharidoses in the severity of the neurologic degeneration compared to the amount of somatic disease. Infants usually appear healthy but developmental delay becomes evident by 2 or 3 years of age and physical growth slows. Deterioration in mental development is progressive and seizures occur in some. Gait and speech are impaired and by age 10 years patients have severe disabilities. Behavioral problems including hyperactivity and aggression are often severe.
There is some hepatosplenomegaly, mild coarseness of the facial features, claw hands and mild bony changes such as biconvexity of the vertebral bodies and thick calvaria. Hirsutism and synophrys are common. The hair is unusually coarse. Joints are frequently stiff and more severely affected individuals may have hearing loss. Diarrhea is frequently a problem and most patients have some airway obstruction and are susceptible to recurrent respiratory infections. Some patients have cardiovascular problems.