Sanfilippo Syndrome

Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is a rare, inherited disorder. Sanfilippo syndrome is classified as a lysosomal storage disorder (LSD). In these disorders, genetic variations disrupt the normal activity of lysosomes in human cells.

Lysosomes contain specific proteins (enzymes) that are responsible for breaking down and recycling molecules such as fats and sugars. Individuals with a lysosomal storage disorder lack one of these necessary enzymes or do not contain one of these enzymes in sufficient quantities to break down molecules for cells to function properly.

Sanfilippo syndrome is divided into four subtypes, which are differentiated by their genetic cause: MPS IIIA, IIIB, IIIC, and IIID. All four subtypes of Sanfilippo syndrome primarily affect the brain and spinal cord. Over time, other body systems can also be affected.

Symptoms of Sanfilippo syndrome can vary significantly depending on the subtype of the disease. Even within a specific subtype, there is a high degree of variation in the number of symptoms and their severity.

Features of MPS IIIA typically appear earlier in life and progress more rapidly than symptoms in other Sanfilippo syndrome subtypes. Children with Sanfilippo syndrome typically do not display any symptoms at the time of birth. Rather, most symptoms begin to develop in early childhood.

Signs and symptoms include:

• Delayed speech
• Behavior problems
• Certain features of autism spectrum disorder (difficulty with communication and social skills)
• Sleep disturbances
• Developmental regression
• Intellectual disability
• Seizures
• Movement disorders
• Mildly coarse facial features
• An enlarged head (site:)
• An enlarged tongue (macroglossia)
• Umbilical hernia or inguinal hernia

Over time, symptoms children might have include:

• Arthritis
• Hearing loss
• Visual impairment
• Enlargement of the liver and spleen (hepatosplenomegaly)
• Frequent respiratory infections
• Chronic diarrhea

In all four subtypes of Sanfilippo syndrome, a genetic variation results in an inability to properly break down a substance known as heparan sulfate, which ultimately builds up in the body’s tissues. Sanfilippo syndrome is inherited in an autosomal recessive pattern, which means that an affected child has received one defective copy of the gene responsible for enzyme production from each of their parents.

There are currently no approved therapies to reverse the effects of Sanfilippo syndrome. Current approaches involve collaboration between specialists to manage specific symptoms of the disease.

At the Boston Children's Lysosomal Storage Disorders (BoLD) Program, our team of providers is committed to the care of complex patients. As part of Boston Children’s Hospital, we are prepared to meet the challenge of providing multifaceted care by partnering with you and your child to deliver direct care in our BoLD clinic. We work with the broad array of world-class specialists at Boston Children’s to optimize the care we provide your child with Sanfilippo syndrome.