This disorder was first reported in 1963 by Dr. Sylvester J. Sanfilippo and coworkers. Sanfilippo syndrome belongs to a group of disorders called mucopolysaccharidoses, so-called because mucopolysaccharides, composed of long chains of sugar molecules, accumulate in cells throughout the body as the result of gene mutations causing enzyme deficiencies. Four types have been described.
The major feature in Sanfilippo syndrome is progressive neurological deterioration. Infants and young children usually appear clinically normal but by the age of 3 years some mental and physical delays are evident. By age 6 years, children have serious difficulties in gait and speech and by 10 years they have severe disabilities. Behavioral problems such as aggression and hyperactivity are common. Seizures often are a feature.
The facial features may be somewhat coarse. Patients have excessive, coarse hair. Feeding and breathing problems are common. The joints are abnormally stiff and some patients have hearing problems. The liver and spleen can be somewhat enlarged. The cornea (windshield of the eye) becomes mildly cloudy and the light sensitive tissue of the eye (retina) is often abnormally pigmented.
DNA defects (mutations) in four genes have been identified and each of these causes Sanfilippo disease. These genes code for enzymes that normally break down long chains of sugar molecules called mucopolysaccharides. Their function is impaired by the mutations and, as a result, these molecules accumulate in cells causing malfunctions. In each case the disorder is inherited in an autosomal recessive pattern when individuals inherit two copies of the mutation. The parents, who each carry one mutation, are clinically normal but they have a 25% risk with each pregnancy of having a child with Sanfilippo syndrome.
The diagnosis is often delayed until 1 to 3 years of age and most likely made by a pediatrician or medical geneticist based on the physical appearance and the presence of developmental delays. There is no treatment for the underlying disease and therapy is usually directed at improvement in quality of life. A multidisciplinary team consisting of pediatricians, neurologists, ophthalmologists, cardiologists, orthopedists, audiologists, and gastroenterologists, is often helpful in addressing all the various issues. A few patients can live to adulthood but most succumb to the disease before the age of 20 years. Enzyme and gene replacement therapies hold promise but as yet are not available.