Living With Sanfilippo

​Dave Esposito is the father of a daughter diagnosed with Sanfilippo syndrome, a rare lysosomal disorder that currently has no treatment or cure. As Dave explains in this interview, the behavioral and neurodegenerative aspects of this rare disease can be stressful for the family.Dave recently took a sabbatical from work to learn more about Sanfilippo and hopefully find a means to treat his daughter before it is too late. What is Sanfilippo disease? 
Children with Sanfilippo syndrome have inadequate levels of specific enzymes needed to metabolize heparan sulfate. This leads to a build up of heparan sulfate in lysosomes that in turn leads to progressive neural degeneration. There are 4 types of Sanfilippo syndrome based on the specific enzyme that is affected. Sanfilippo Type A: heparan N-sulfatase. Sanfilippo Type B: alpha-N-acetylglucosaminidase. Sanfilippo Type C: acetyl-CoAlpha-glucosaminide acetyltransferase. Sanfilippo Type D: N-acetylglucosamine 6-sulfatase.

What is Sanfilippo?

MPS III is a mucopolysaccharide disease also known as Sanfilippo syndrome. It takes its name from Dr. Sylvester Sanfilippo, one of the U.S. doctors who described the condition in 1963.

​What causes this disease?
Mucopolysaccharides are chains of sugar molecules used to build connective tissues in the body.
  • “muco” refers to the thick jelly-like consistency of the molecules
  • “poly” means many
  • “saccharide” is a general term for a sugar molecule
The body constantly replaces used materials and breaks them down for disposal. MPS III patients are missing an enzyme essential to breaking down the mucopolysaccharide heparan sulphate. These materials remain stored in the body’s cells, causing progressive damage. Babies may show little sign of the disease, but as cells sustain damage, symptoms start to appear.

Are there different forms of this disease?
To date, four different enzyme deficiencies have been found to cause MPS III, described as type A, B, C or D.
There is usually little difference between the four types, but some mild cases of the B form saw affected individuals stay relatively healthy into adult life.

How common are these diseases?
MPS III is the most common form of mucopolysaccharidosis, and 1 in 70,000 newborns are born with the disease. MPS III A and MPS III B are more common than MPS III C and MPS III D.

How is the disease inherited?
MPS III is caused by a recessive gene. There is a one in four chance with every pregnancy that the child will inherit the defective gene from each carrier parent and will be affected with the disease. There is a two in three chance that unaffected brothers and sisters of MPS III patients will be carriers.

Is there a cure?
There is no cure for MPS III and no current approved treatment. Enzyme replacement therapy (ERT) has not been shown to be effective in MPS III. Bone marrow transplants have been tried on individuals with MPS III, but with disappointing results. Gene therapy, chaperone therapy and intrathecal enzyme therapy are a few of the treatments for MPS III where research is ongoing.
How does the disease progress?The disease affects each person differently, and its progress will be much faster in some individuals than in others. Symptoms often appear after age 1, and learning abilities begin to slow between ages 2 and 6. Normal growth continues during the first few years, but will begin to slow, and final height is below average. Delayed development is followed by worsening mental status.
Other symptoms include:
  • Behavioral problems
  • Coarse facial features
  • Diarrhea
  • 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

Information taken from National MPS society
What are the main signs and symptoms of Sanfilippo syndrome?

Many of the first signs of Sanfilippo syndrome are related to the central nervous system, which is the complex system of nerve tissues that control the activities of the body. Signs and symptoms may include:

  • Speech delay
  • Developmental difficulties, including a delayed ability to learn
  • Behavioural problems, such as restlessness, hyperactivity, anxiety and aggression
  • Sleep difficulties, sometimes so severe that children may only sleep for a few hours a night
  • Problems walking


Over time, people with Sanfilippo syndrome gradually lose skills and abilities they may have had previously, including speech, walking and the ability to eat. 


Some people with Sanfilippo syndrome may display symptoms similar to those seen in autism spectrum disorder, which usually affects communication and social interaction. In a study looking at autistic behaviours in children with Sanfilippo syndrome, the researchers found that 13 of the 21 children studied met the criteria for an autism diagnosis. 


It is important to minimize delays in establishing a proper diagnosis of Sanfilippo syndrome. It may take many years to find the correct diagnosis, as children may be misdiagnosed with attention deficit hyperactivity disorder or autistic spectrum disorder. Some researchers suggest that children with early psychiatric or behavioral problems should be tested for possible underlying metabolic problems, such as MPS III. 


Physical symptoms
Children with Sanfilippo syndrome may also show physical symptoms, although these are often less obvious than the central nervous system symptoms described above. These symptoms may include: 

  • Course facial features
  • An enlarged head (macrocephaly)
  • A slightly enlarged liver (mild hepatomegaly)
  • An out-pouching around the belly button (umbilical hernia)
  • Joint stiffness
  • Short height
  • Abnormalities in the skeleton that appear on x-ray
  • Long-term diarrhea 
  • Breathing difficulties
  • Frequent ear infections 
  • Hearing loss or vision problems

How do the symptoms of Sanfilippo syndrome progress?

Children with Sanfilippo syndrome do not usually show symptoms from birth. They typically begin to show symptoms of the condition during early childhood, from the ages of about one to three years old. Symptoms will get progressively worse over time. Progression of the disease is different for each individual.   


Typically, behavioral problems will start to get worse between the ages of three and five, and can become severe. This may include symptoms such as hyperactivity, which is often violent or aggressive, as well as progressive sleep disturbance. 


Patients often experience these symptoms for about five to 10 years, after which behavioral issues may become less pronounced. At this point, processes such as speech or motor activities like walking or eating may be affected. This decline in symptoms continues progressively to a point where patients will need constant care. 

What symptoms impact individuals with Sanfilippo syndrome the most? 

In a recent study conducted by Raremark, member of the Sanfilippo community were asked to share the symptoms that affect them, particularly which symptoms affect them the most. These insights are important as they can help researchers understand what living with a rare condition is like, and may help to inform future treatment developments. 


The results of this survey showed the most common first symptoms experienced were behavioral difficulties, sleep problems and intellectual decline, as well as diarrhea and ear infections. The symptoms that affected individuals with Sanfilippo the most were behavioral problems and sleep difficulties. Seizures were also a major problem requiring frequent monitoring. 

Sources:  Main Source: https://raremark.com/sanfilippo-syndrome-mps-iii/articles/signs-symptoms--704