Sanfilippo syndrome

background

Sanfilippo syndrome is an inherited disease that belongs to a group of diseases called mucopolysaccharidoses (MPS). Specifically, it is known as MPS type 3. Mucopolysaccharides are complex sugar molecules that are constantly used and broken down in the body. In 1963, Dr. Sylvester Sanfilippo was one of the first doctors to describe Sanfilippo syndrome.
In individuals with Sanfilippo syndrome, one of the enzymes that break down heparan sulfate, a carbohydrate, or complex sugar molecule, that inhibits blood clotting, is missing or malfunctioning. This causes heparan sulfate to buildup to abnormally high levels in lysosomes, which are the compartments in the cell responsible for breaking down and disposing of cell waste. Waste products that buildup in lysosomes are excreted in the urine, so individuals with Sanfilippo syndrome tend to have high levels of heparan sulfate in their urine.
Because of the buildup of heparan sulfate, cells do not function properly. Symptoms of Sanfilippo syndrome include problems with the heart, bones, joints, and lungs. As the disease progresses, this buildup of heparan sulfate in nerve cells causes serious problems resulting from the failure of the nervous system.
It is estimated that Sanfilippo syndrome affects one out of every 80,000 births. Males and females are affected in equal numbers. The disease may not be apparent at birth. Signs and symptoms progress with age as heparan sulfate accumulates and damages cells and organs. Most people with Sanfilippo syndrome live into their teenage years. Some patients live longer, while others with severe forms die at an earlier age from complications.
There are four types of Sanfilippo syndrome: types A, B, C, and D. Each type is caused by mutations in one of the four genes that provide instructions for making enzymes involved in breaking down heparan sulfate. Depending on the type of Sanfilippo syndrome, the mutation could occur in the gene for heparan sulfate sulfatase (type A), alpha-N-acetylglucosaminidase (type B), acetyl-CoA alpha-glucosaminide N-acetyltransferase (type C), or N-acetylglucosamine 6-sulfatase (type D).

Related Terms

Acetyl-CoA alpha-glucosaminide N-acetyltransferase deficiency, glycosaminoglycans, heparan sulfate, heparan sulfate sulfatase deficiency, lysosomal storage disease, MPS III, MPS type 3, mucopolysaccharides, mucopolysaccharidosis III, mucopolysaccharidosis type 3, N-acetylglucosamine-6-sulfate sulfatase deficiency, N-acetylglucosaminidase deficiency.

types of the disease

There are four main types of Sanfilippo syndrome, which is also called mucopolysaccharidosis type 3 (MPS III). There are four different genes that, when mutated or defective, provide incorrect instructions for making enzymes that break down heparan sulfate. These incorrect instructions result in enzymes that cannot adequately break down heparan sulfate. The gene and enzyme that are affected determine the type of Sanfilippo syndrome.
Sanfilippo type A: Type A is the most severe form of Sanfilippo syndrome. In this type of the disease, the enzyme heparan sulfate sulfatase is altered or absent.
Sanfilippo type B: In type B Sanfilippo syndrome, the enzyme alpha-N-acetylglucosaminidase is absent or deficient. Type B is generally milder than type A. On average, symptoms of type B start to appear between 40 and 60 years of age and may include heart disease, arthritis, skin blistering, swallowing problems, seizures, and behavioral problems (restlessness, screaming, and hitting). One study in the Netherlands showed that type B is the most common subtype of mucopolysaccharidosis in that country. It is believed that type B is underdiagnosed in adults with mental disabilities.
Sanfilippo type C: In type C Sanfilippo syndrome, the enzyme acetyl-CoA alpha-glucosaminide N-acetyltransferase is absent or inadequate.
Sanfilippo type D: In type D Sanfilippo syndrome, the enzyme N-acetylglucosamine 6-sulfatase is absent or deficient.