Definition:
Sanfilippo type A/MPS III A is caused by a mutated gene that manufactures the enzyme heparan sulfatase. This enzyme is needed to break down a specific type of sugar or mucopolysaccharides called heparan sulfate. The enzyme, heparan sulfatase, is either produced in very low amounts or is completely absent in individuals afflicted with Sanfilippo type A/MPS III A. The sugars are used to build connective tissues in the body. Individuals affected with Sanfilippo type A/MPS III A have too much heparan sulfate in their system. Excessive amounts of the sugars lead to the clinical symptoms of Sanfilippo type A/MPS III A.

There are four types of Sanfilippo/MPS III: A, B, C, and D. The four forms of this disorder have very little clinical differences. The differing characteristic is the specific gene that codes for the specific enzyme. The incidence of all four together is estimated at one in 70,000 births worldwide. Type A is the most common form of this disorder in Northwestern Europe.

Symptoms:
Children born with Sanfilippo type A/MPS III A appear normal, but as more cells become damaged, the signs and symptoms associated with the disorder begin to appear. Symptoms are progressive and classified in stages based upon those presented. Behavioral problems associated with this disorder appear around two years of age.

In the initial stage, the affected child will display delayed speech skills as well as some mild facial abnormalities. In the following stage, the affected child will become extremely active, restless, suffer sleeplessness and exhibit difficult behavior. Many chew on their hands, clothes, or on other items. Over time, speech and comprehension will diminish. By age six, most children will develop severe mental retardation. By age 10, the affected child’s movement will become very limited. In the final stage, this child will become immobile and generally unresponsive.

Although most of the symptoms are neurological in nature, some children affected may also develop diaherra, cavities and an enlarged liver and spleen. Another physical chacteristic of this disorder is an abundance of coarse hair.

Inheritance Pattern:
Sanfilippo type A/MPS III A is an autosomal recessive disorder.

Life Expectancy:
Current life expectancy is 14 to 20 years of age.

Diagnois and Testing:
A urine test is utilized to diagnose Sanfilippo type A/MPS III A, by measuring increased levels mucopolysaccharides, the type of sugar chain in the lysosome that accumulates as a result of the malfunctioning enzyme. A urine test is routinely followed by a blood test or skin biopsy, which will show reduced activity of the enzyme heparan sulfatase. Prenatal screening is available to examine heparan sulfatase activity in the fetus. Genetic testing is also available in combination with these diagnostic tests to look for the mutation that causes Sanfilippo type A/MPS III A.

Treatment:
There is no cure for Sanfilippo type A/MPS III A. If the disease is caught early, bone marrow transplantation may be beneficial in slowing down its progression. In most cases, treatment is limited to reducing or controlling symptoms of this disorder. Medications to control behavioral problems have not been proven to be effective. Anti-convulsant medication is often prescribed to control seizures, devices are inserted into the affected child’s mouth to help with swallowing difficulties, and wheelchairs are often required as the disorder progresses to its final and immobile stage. Genetic counseling is also encouraged.

Since gene therapy is currently being investigated in animal studies, there is great hope that this procedure will produce a cure for this disorder in the coming years. Other potential treatments are enzyme replacement therapies that cross the blood-brain barrier, therefore allowing the neurological symptoms to be treated. Stem cell transplants are also another mode of treatment currently under investigation. It is accepted within the medical community that a diagnosis made very early in the course of the disorder may render treatment more effective than it might be following a later diagnosis.

Patient Groups:
National MPS Society
4220 NC Highway 55, Suite 140
Durham NC, 27713
www.mpssociety.org
tel: (919) 806-0101
fax: (919) 806-2005
Barbara Wedehase, Executive Director
info@mpssociety.org