Sanfilippo Syndrome is caused by a defect in a single gene. 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.

Combined, the four types of Sanfilippo, presents in approximately 1 in 70,000 births.

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 that children start to show delays; 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.  They are often misdiagnosed as Autistic.  Affected children are prone to frequent sinus infections, ear infections and chronic diarrhea.  They may have cavities or chipped teeth from weak enamel and headaches from accumulated fluid pressure on the brain.  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, frontal lobe blossoming.

Second stage: The affected child will become overly active, often diagnosed with ADHD or extreme oppositional defiant disorder.  They’re restless, suffer from sleeplessness and exhibit difficult behavior. Irrational fears are common, or they seem to have no fear, they will run into the street to avoid walking by a dog on the sidewalk. Many children are compelled to chew on things- doctors may diagnose this as a sensory processing disorder.  They may experience major temper tantrums accompanied by inconsolable behavior and compulsive behavior; grabbing at people or items, screaming for no apparent reason, laughing fits.  Some children have seizures others have visual and hearing problems.  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. Children often succumb to pneumonia or other types of infections. A few cases of those with attenuated forms of Sanfilippo have been reported to live to the 3rd or 4th decade of life, but with a poor quality of life.