Sanfilippo Syndrome is caused by a defect in a single cell. It is an inherited disease of metabolism that means the body cannot properly break down long chains of sugar molecules called mucopolysaccharides or glycosaminoglycans (aka GAGs). Sanfilippo syndrome belongs to a group of diseases called mucopolysaccharidoses (MPS). Specifically, it is known as MPS III.

Sanfilippo Syndrome occurs when the enzymes the body needs to break down the Heparan Sulfate (HS) are absent or are defective. When HS is not broken down, the body does not release it. Instead, it is stored inside the lysosomes of every cell in the body.
This is why Sanfilippo Syndrome is classified as a Lysosomal Storage Disease (LSD). As the GAGs accumulate, they damage the cells they are stored in. This leads to the progressive degeneration of the central nervous system.

To date there are four types of Sanfilippo syndrome. They are distinguished by the enzyme that is affected.

  • Sanfilippo Type A: heparan N-sulfatase. Estimated incident rate is 1 in 100,000 live births.
  • Sanfilippo Type B: alpha-N-acetylglucosaminidase. Estimated incident rate is 1 in 200,000 live births.
  • Sanfilippo Type C: acetyl-CoAlpha-glucosaminide acetyltransferase. Estimated incident rate is 1 in 1,400,000.
  • Sanfilippo Type D: N-acetylglucosamine 6-sulfatase. Estimated incident rate is 1 in 1,100,000.

Between the four types of Sanfilippo, the syndrome present in approximately 1 in 70,000 births.

What happens to a child with Sanfilippo Syndrome?

Sanfilippo is an insidious disease that often goes undetected for years. Most children are born with no visible signs that anything is wrong. It’s not until the preschool years (or later with some type C cases) that children start to show delays or deformities; even then, the disease is often misdiagnosed. Highly specialized and focused testing must be done in order to diagnose Sanfilippo.

Sanfilippo is progressive and can be broken down into stages.

First stage: The affected child will display delayed speech as well as mild facial abnormalities and behavioral issues. Some children will exhibit a large head, prominent forehead, bushy eyebrows, coarse thick hair, thick skin, short neck, full lips, low thick ears, low nasal bridge and full round bellies. Their facial features are described as “coarse.” Affected children are prone to frequent sinus and ear infections, diarrhea, and tight Achilles tendons. They may have cavities or chipped teeth from weak enamel and headaches from accumulated fluid pressure.  Children may seek input demonstrated by vestibular stimulation. Minor bone deformities like a raised sternum and flared ribs are quite common.  Children have large head circumferences, due to a skull deformity, clinically called a J Shaped Sella Turcica.  The problems associated with Sanfilippo are vast and varied.

Second stage: 
The affected child will become extremely active, restless, suffer sleeplessness and exhibit difficult behavior. Many children are compelled to chew on things- doctors may diagnose this as a sensory processing disorder.  Major temper tantrums accompanied by inconsolable behavior.  Difficult behavior: grab at people or items, screaming for no apparent reason, laughing fits.  Some children have seizures others have visual and hearing problems.  Again, these symptoms vary from child to child. Over time, speech loss occurs  and communication skills decline along with cognitive regression and loss of motor skills.

Third stage: The disease will take its ultimate toll. The child will lose the ability to walk, talk and eat on his own while his body shuts down. Death may occur as early as the age of three. More common, however, are children that live into their early teens, with some surviving into their twenties. A few cases of those with mild forms of Sanfilippo have lived into their early thirties.

Currently there is no cure for Sanfilippo Syndrome. In most cases, treatment is limited to reducing or controlling the symptoms of this disorder by making sure that neurologists, ophthalmologists, cardiologists, ENTs, orthopedicians, dentists and genetic counselors are consulted routinely.
Medications to control the behavioral problems associated with this disorder have not proven effective. Anti-convulsant medication may control seizures, devices can be inserted in the mouth to assist swallowing, and wheelchairs are often required as the disorder progresses to its final and immobile stage.
Genetic counseling is encouraged. Controlling the diet can be helpful – for example, removing dairy and gluten products to help reduce mucus secretions. Early Intervention services such as Speech, Occupational Therapy and Physical Therapy are also very beneficial for the children.