Sanfilippo syndrome is metabolism disorder passed down through families. It makes the body unable to properly break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides).
The syndrome belongs to a group of diseases called mucopolysaccharidoses (MPS). Specifically, it is known as MPS III.
Sanfilippo syndrome occurs when the substances (enzymes) needed to break down the heparan sulfate sugar chain are missing or are defective.
There are four main types of Sanfilippo syndrome, also called MPS III. Which type a person has depends on which enzyme is affected.
- Sanfilippo type A is the most severe form. Persons with this type are missing or have an altered form of an enzyme called heparan N-sulfatase.
- Sanfilippo type B occurs when a person is missing or does not produce enough alpha-N-acetylglucosaminidase.
- Sanfilippo C occurs when a person is missing or does not produce enough acetyl-CoAlpha-glucosaminide acetyltransferase.
- Sanfilippo D occurs when a person is missing or does not produce enough N-acetylglucosamine 6-sulfatase.
The syndrome is inherited as an autosomal recessive
trait. If both parents carry the defective gene related to this condition, each of their children has a 25% chance of developing the disease.
Sanfilippo syndrome is possibly the most common forms of MPS. It is seen in about 1 in 70,000 births. A family history of Sanfilippo syndrome increases the risk for this condition.
Unlike many other forms of MPS, symptoms often appear after the first year of life. A decline in learning ability typically occurs between ages 2 and 6. The child may have normal growth during the first few years, but final height is below average. Delayed development is followed by deteriorating mental status.
Other symptoms include:
- Behavioral problems
- Coarse facial features
- Full lips
- Heavy eyebrows that meet in the middle of the face above the nose
- Sleep difficulties
- Stiff joints that may not extend fully
- Walking problems
Exams and Tests
A physical exam may show signs of liver and spleen swelling. An eye exam will show clear corneas, unlike the cloudy corneas seen in persons with Hurler syndrome (MPS I H). Neurological testing will reveal signs of seizures and intellectual disability.
Urine tests will be done. Persons with Sanfilippo syndrome have large amounts of a mucopolysaccharide called heparan sulfate in the urine.
Other tests may include:
Skin fibroblast culture
X-rays of the bones
There is no specific treatment available for Sanfilippo syndrome.
The syndrome causes significant neurological symptoms, including severe intellectual disability. IQs may be below 50. Most persons with Sanfilippo syndrome live into their teenage years. Some patients live longer, while others with severe forms die at an earlier age. Symptoms appear most severe in persons with type A Sanfilippo syndrome.
- Inability to care for self
- Intellectual disability
- Nerve damage that slowly gets worse and eventually requires wheelchair use
When to Contact a Medical Professional
Call your health care provider if your child does not seem to be growing or developing normally.
Call for an appointment with your health care provider if you plan to have children and you have a family history of Sanfilippo syndrome.
Genetic counseling is recommended for prospective parents with a family history of Sanfilippo syndrome. Counseling is also recommended for families who have a child with Sanfilippo syndrome, to help them understand the condition and possible treatments. Prenatal testing is available.
Wraith JE. Mucopolysaccharidoses and oligosaccharidoses. In: Saudubray J-M, van den Berghe G, Walter JH, eds. Inborn Metabolic Diseases: Diagnosis and Treatment. 5th ed. New York, NY: Springer; 2012:chap 40.
Chad Haldeman-Englert, MD, FACMG, Wake Forest School of Medicine, Department of Pediatrics, Section on Medical Genetics, Winston-Salem, NC. Review provided by VeriMed Healthcare Network. Also reviewed by David Zieve, MD, MHA, Bethanne Black, and the A.D.A.M. Editorial team.