Sanfilippo syndrome, also called mucopolysaccharidosis (MPS) type III, is a genetically inherited metabolic disorder that causes nervous system issues and other symptoms in children.

This syndrome is also sometimes referred to as “childhood Alzheimer’s” because it ultimately causes a loss of physical and mental development over time.

Researchers estimate fewer than 5,000 people in the United States have Sanfilippo syndrome. Keep reading to find out more about this rare disorder, what causes it, and what symptoms you may observe in your child.

Sanfilippo syndrome is a lysosomal storage disorder. What this means is that it affects enzymes responsible for breaking down and recycling certain carbohydrates called heparan sulfates.

When these complex sugar molecules build to high levels in the body, they damage the brain and central nervous system. The disorder may also cause a number of other symptoms, ranging from excessive hair growth to chronic ear infections and more.

The types of Sanfilippo syndrome are each caused by mutations in different genes:

  • Type A: Caused by a deficiency in heparan-N-sulfatase, type A is the most common. It occurs in 1 in 100,000 births. It’s the most severe form of Sanfilippo syndrome.
  • Type B: Caused by a deficiency in alpha-N-acetylglucosaminidase, this type is also common. It occurs in 1 in 200,000 births.
  • Type C: Caused by a deficiency in acetyl-co-alpha-glucosaminide acetyltransferase, this type is less common. It occurs in 1 in 1.5 million births.
  • Type D: Caused by a deficiency in N-acetylglucosamine-6-sulfatase, this type is also less common. It occurs in 1 in 1 million births.

Sanfilippo syndrome is an autosomal recessive disorder. This means it can be genetically passed from parents to children during conception.

If both genetic parents of a child are carriers of the syndrome, with each pregnancy they have a:

  • 25% chance of having a child with Sanfilippo syndrome
  • 50% chance of having a child who is not affected but is a carrier
  • 25% chance of having a child who is neither affected nor a carrier

Babies born with Sanfilippo syndrome may not have any signs of it at birth. Symptoms typically begin when a child is between 2 and 5 years old.

The onset and progression of symptoms can vary based on the child:

  • Children between the ages of 1 and 3 years old may show early signs, which include delays with motor development and language.
  • Children between the ages of 3 and 10 years old may have these delays as well as sleep issues and hyperactivity, aggression, or other behavioral issues.
  • Older children over 10 years old may show further signs of Sanfilippo, which include loss of motor skills and previous milestones, like toilet training and language skills. Seizures and trouble walking are other signs in this age group.

After its initial onset, the syndrome is progressive, meaning its effects may get worse over time. It affects multiple body systems, physical features, and behaviors. Symptoms can range from mild to severe and be life threatening.

Physical characteristics

  • Facial features:
    • thickened lips
    • large tongue
    • big eyes
    • flat face
    • bushy, dark eyebrows
    • widely spaced teeth
  • Hair: hirsutism (thick hair and excessive hair growth)
  • Head: macrocephaly (an enlarged head)
  • Height: below average to average height
  • Abdomen: distended or protruding stomach
  • Feet and legs:

Nervous system symptoms

The majority of the effects of Sanfilippo syndrome involve the central nervous system.

Symptoms include:

Gastrointestinal symptoms

  • frequent diarrhea
  • hepatosplenomegaly (swelling of the liver and spleen)
  • umbilical hernia (near the belly button) or inguinal hernia (in the groin)
  • issues metabolizing medications

Musculoskeletal symptoms

Eye symptoms

Ear, nose, and throat symptoms

Cardiovascular symptoms

Congenital heart defects are not as common with Sanfilippo syndrome as they are with other forms of MPS.

Symptoms include:

Questions for your doctor or healthcare professional

There’s a lot to know and understand about Sanfilippo syndrome. Consider preparing for your next appointment by jotting down some questions to ask your child’s doctor.

You might ask:

  • What type of Sanfilippo syndrome does my child have?
  • What kind of specialized medical care might my child need?
  • What other kinds of support may help my child (e.g., physical therapy, occupational therapy, speech therapy, etc.)?
  • What investigational treatments and clinical trials are available to my child?
  • What are the chances my partner and I may pass along the syndrome in a future pregnancy?
  • Where can my family find social support and other resources for Sanfilippo syndrome?

Doctors can make a diagnosis of Sanfilippo syndrome by observing symptoms and physical characteristics as well as ordering tests.

These tests may include:

  • Laboratory tests: These may first involve a urine test (urinalysis) to measure heparan sulfate levels in the urine. A blood test or skin test can further confirm the results by measuring enzyme activity.
  • Imaging tests: These may include MRI to check for brain abnormalities, X-rays to examine physical signs, and an echocardiogram to determine heart defects.

Doctors can also diagnose Sanfilippo syndrome before a child is born with prenatal genetic testing. Options include amniocentesis and chorionic villus sampling (CVS) testing.

The medical team that may treat a child with Sanfilippo syndrome

If your child is diagnosed with Sanfilippo syndrome, your pediatrician will refer you to a children’s hospital for more specialized care. You will likely work with a team of doctors to address your child’s various health needs. This team of specialists may include a:

  • Neurologist: a doctor who specializes in issues with the brain and nervous system
  • Developmental-behavioral pediatrician: a doctor who specializes in learning and behavior issues in children
  • Metabolic geneticist: a doctor who specializes in genetically inherited metabolic disorders
  • Orthopedist: a doctor who specializes in issues with the musculoskeletal system
  • Gastroenterologist: a doctor who specializes in issues with the digestive system
  • Ophthalmologist: a doctor who specializes in issues with the eyes
  • Cardiologist: a doctor who specializes in issues with the heart and greater cardiovascular system
  • Endocrinologist: a doctor who specializes in issues with hormones, growth, and metabolism
  • Otolaryngologist: a doctor who specializes in issues with the ear, nose, and throat
  • Additional support: physical therapists, occupational therapists, behavioral therapists, speech therapists, etc.

There is no cure for Sanfilippo syndrome. Treatment is focused on improving quality of life and treating specific symptoms as they occur.

Treatment may also include physical therapy, occupational therapy, and exercise to help with joint issues and overall mobility.

These potential treatments are currently in clinical trials:

  • Gene therapy uses a virus to supply a normal copy of the abnormal gene to the body.
  • Enzyme replacement therapy replaces the missing enzymes needed to break down heparan sulfate.
  • Stem cell therapy involves taking stem cells from the bone marrow. The stem cells are specially developed to overproduce the missing enzyme and target the cells that travel into the brain. The enzyme is then taken up by affected brain cells and starts correcting the extra storage of heparan sulfate. (Stem cell therapy for Sanfilippo is currently in the pre-clinical trial stage.)

The outlook for children with Sanfilippo syndrome depends on various factors, including which type a child has and the medical care a child receives.

In general, children experience significant neurological symptoms and IQ levels that may be 50 or below.

The life expectancy ranges may vary as well. The average person with Sanfilippo syndrome may live to be between 15 and 20 years old. Some people may live into their 30s or 40s. Others, particularly children with Sanfilippo type A, may not live beyond age 10.

Sanfilippo syndrome is a rare disorder that’s passed down in families through genes. While symptoms do not show up at birth, they develop in early childhood and cause a regression in development as well as other physical and behavioral symptoms.

Researchers are working on new therapies that may address the altered genes or restore healthy enzyme activity. Your child’s doctor can help answer the questions you have about your child’s symptoms, possible treatment options, and support for an improved quality of life.