Mucopolysaccharidosis Type III
What is mucopolysaccharidosis type III?
Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a genetic condition in which a person is unable to break down large sugar molecules known as a glycosaminoglycans (GAGs). In MPS III, a specific GAG called heparan sulfate is unable to be broken down and builds up over time. Patients with MPS III usually appear normal at birth. Children may meet milestones up until age 2-6 and then start showing abnormal behaviors that get worse as the child gets older. At approximately 3-5 years of age most patients begin to develop mental and motor developmental delay, resulting in mental retardation. By age 10 other symptoms appear including wobbly and erratic gait and difficulty walking, aggressive behavior, stiff joints, skeletal abnormalities, hernias, enlarged liver and/or spleen (hepatosplenomegaly), hyperactivity, seizures, deafness, loss of vision, progressive dementia, and an inability to sleep for more than a few hours at a time. Most people with MPS III may survive into their teenage years, though some can survive into their twenties.
There are four different subtypes of MPS III, caused by changes/mutations in one of four different genes:
- MPS IIIA (caused by a change or mutation in the SGSH gene)
- MPS IIIB (caused by a change or mutation in the NAGLU gene)
- MPS IIIC (caused by a change or mutation in the HGSNAT gene)
- MPS IIID (caused by a change or mutation in the GNS gene)
Each of these genes is supposed to make an enzyme responsible for breaking down heparan sulfate. If a gene has a change or mutation, then the enzyme it is responsible for making doesn't work as well as it should. All subtypes of MPS III are inherited in an autosomal recessive manner. This means that a person affected with MPS III has a change or mutation in both copies of a particular gene and therefore has no working copies of the gene that causes this syndrome.
The best person to figure out if someone may have MPS III is a geneticist (doctor with special training in genetics), or other doctor with special training and experience in MPS disorders. You can ask your primary doctor for a referral or recommendation. The American College of Medical Genetics and Genomics (ACMG) also has a "Find a Genetics Clinic" search function that can help you find a genetics specialist near you. ACMG Find a Genetic Service