Sanfilippo Syndrome

What is Sanfilippo syndrome?

Sanfilippo syndrome is a group of inherited (genetic) lysosomal storage disorders that mainly affect your child’s central nervous system (brain and spinal cord). It causes a variety of cognitive (mental), behavioral and physical symptoms that get worse over time. These symptoms lead to premature death.

Another name for this condition is mucopolysaccharidosis type III (MPS III).

Sanfilippo syndrome happens when there’s a deficiency in one of four enzymes that affect the breakdown (metabolism) of heparan sulfate. Heparan sulfate is a glycosaminoglycan (also known as a mucopolysaccharide), a complex carbohydrate. Because your child doesn’t have the proper enzyme to break down heparin sulfate, it builds up in their cells, tissues and organs, damaging them.

Sanfilippo syndrome types

There are four subtypes of Sanfilippo syndrome: types A, B, C and D. Each subtype results from a deficiency of a different enzyme:

• Type A: Sulfamidase deficiency.
• Type B: α-N-acetylglucosaminidase deficiency.
• Type C: Heparan acetyl CoA: α-glucosaminide N-acetyltransferase deficiency.
• Type D: N-acetylglucosamine 6-sulfatase deficiency.

How common is Sanfilippo syndrome?

Sanfilippo syndrome is rare. Researchers estimate that it affects 1 person per every 50,000 to 250,000 people. Sanfilippo syndrome type A is the most common subtype globally. Type D is the least common.

What are the symptoms of Sanfilippo syndrome?

Symptoms — and their severity — can vary for Sanfilippo syndrome due to the different types. Early signs and symptoms of the syndrome in newborns and infants may include:

• Coarse facial features.
• Prominent, broad eyebrows.
• Excessive body hair (hirsutism) that doesn’t go away.
• A head that’s larger than typical (macrocephaly).
• Sleep disturbances.
• Respiratory problems, like ear and/or nasal congestion and breathing difficulties.
• Colic-like episodes.
• Frequent diarrhea.

You may or may not notice these initial signs. As your child ages, they’ll develop more signs of Sanfilippo syndrome. These symptoms typically appear between the ages of 1 and 4.

Neurological and behavioral signs include:

• Speech and language delay (one of the most common first symptoms).
• Non-specific developmental delay.
• Intellectual disability that gets worse with time.
• Aggressive or destructive behavior.
• Hyperactivity.
• Temper tantrums.
• Lack of fear of danger.
• Excessive chewing, sucking, biting or swallowing (hyperorality).
• Restlessness.
• Sleeping issues, like sleep anxiety, parasomnias and sleep apnea.
• Gait (walking) disorders, like toe walking.
• Spasticity.
• Seizures.

Ear, nose and throat symptoms include:

• Hearing loss.
• Recurrent ear infections (otitis).
• Chronic nasal congestion.
• Need for adenoid and tonsil removal (adenotonsillectomy) earlier than usual.

Other symptoms include:

• Diarrhea or chronic loose stools.
• Constipation.
• Abdominal discomfort.
• Abnormal heartbeat (arrhythmia).
• Cardiomyopathy.
• Joint stiffness.
• Scoliosis.

What causes Sanfilippo syndrome?

Sanfilippo syndrome is a lysosomal storage disease (LSD). These are genetic conditions that cause a buildup of toxic substances in your body’s cells. People with LSD lack certain enzymes. Without functioning enzymes, your body can’t break down certain substances. If they build up in your body, it can be harmful.

In the case of Sanfilippo syndrome, one of four enzymes that affect the breakdown of heparan sulfate is missing. Heparan sulfate builds up in cells and damages them. This buildup has the greatest effect on cells in your child’s brain.

Genetic mutations (changes) cause a lack of certain enzymes in Sanfilippo syndrome — specifically, alterations to the SGSH gene.

You inherit these gene alterations from your biological parents in an autosomal recessive pattern. This means that both of your parents passed on the altered gene (they’re carriers) that causes Sanfilippo syndrome. People who are just carriers of the altered gene typically don’t have symptoms of the condition.

How is Sanfilippo syndrome diagnosed?

Sanfilippo syndrome diagnoses tend to be delayed due to how rare the syndrome is and because its symptoms can mimic those of other conditions. Healthcare providers often misdiagnose Sanfilippo syndrome as developmental delay, attention-deficit/hyperactivity disorder (ADHD) and/or autism.

Your child’s provider will do a physical exam and a neurological exam. They’ll also ask about your child’s symptoms and medical history. They may request a variety of tests to rule out certain conditions.

Tests that can help confirm the diagnosis of Sanfilippo syndrome include:

• GAG urine test: This test looks for GAG (glycosaminoglycans) in a sample of your child’s pee.
• Enzyme analysis: This test measures the activity of certain enzymes in a blood sample.
• Genetic testing: This test can look for known genetic mutations (changes) linked to Sanfilippo syndrome.

Your child’s provider may recommend other tests to check for damage to your child’s organs or tissues. These tests may include:

• Brain MRI.
• Eye exam.
• Hearing test.
• Heart tests, like echocardiogram and electrocardiogram (EKG).
• Sleep study.
• X-ray.

Prenatal diagnosis

If you have a family history of Sanfilippo syndrome, your healthcare provider may recommend prenatal testing to check the fetus for the syndrome. This may be possible with amniocentesis or chorionic villus sampling.

What is the treatment for Sanfilippo syndrome?

There’s no cure for Sanfilippo syndrome, and there currently aren’t any disease-modifying therapies available. The main forms of treatment are symptom management and palliative care. Because the syndrome affects many aspects of your child’s health, they’ll have a team of specialists who will collaborate on their care. This team may include:

• Pediatricians.
• Pediatric neurologists.
• Physical therapists.
• Occupational therapists.
• Speech-language pathologists.
• Otolaryngologists (ear, nose and throat specialists).
• Child psychologists.
• Social workers.
• Special educators.

These specialists will recommend treatments, like medications, therapies and assistive devices, based on your child’s unique needs. The main goals of treatment are to maintain your child’s bodily functions, optimize their abilities and maximize their quality of life.

Your child may be able to participate in a clinical trial. Ask your child’s healthcare team if this is an option. Researchers are currently studying disease-specific therapies for Sanfilippo syndrome, like:

• Enzyme replacement therapy.
• Stem cell transplantation.
• Gene therapy.

In the later stages of the syndrome, maintaining quality of life and preventing complications become the priorities of care.

Can I prevent Sanfilippo syndrome?

As Sanfilippo syndrome is genetic, there’s nothing you can do to prevent it.

If you’re concerned about the risk of passing on Sanfilippo syndrome or other genetic conditions before trying to have a biological child, talk to a healthcare provider about genetic counseling.

What can I expect if my child has Sanfilippo syndrome?

If your child has Sanfilippo syndrome, you can expect many healthcare appointments and tests. It can be overwhelming to get a grasp on this complex condition. But know that your child’s healthcare team will be by your side. Because Sanfilippo syndrome affects everyone differently, your child’s team will be your best resource for estimating what the future looks like for your child and family.

In the later phase of Sanfilippo syndrome, your child will likely develop:

• A decline in engagement with their environment.
• Dementia.
• Loss of movement (motor) function, like walking, speaking and eating.

These health issues get worse with time and eventually lead to death. Respiratory tract infections, especially pneumonia, are the most common cause of death.

What is the life expectancy of someone with Sanfilippo syndrome?

In a study analyzing 113 cases of Sanfilippo syndrome, the average life expectancy was:

• Type A: 11 to 19 years.
• Type B: 12 to 16 years.
• Type C: 14 to 32 years.

Type D is very rare, so there’s not enough information on it.

It’s important to remember that each child with Sanfilippo syndrome is different. Your child’s healthcare team will give you a better idea of what to expect and how the syndrome will affect your child’s health.

How do I take care of my child if they have Sanfilippo syndrome?

If your child has Sanfilippo syndrome, it’s important to advocate for them to ensure they get the best medical care. Advocating for care can help them have the best possible quality of life.

You and your family may also want to consider joining a support group to meet others who can relate to your experiences.

Neurodegenerative conditions like Sanfilippo syndrome can have a strong negative impact on your and your family’s mental health and quality of life. Parents and caregivers of children with Sanfilippo syndrome are at increased risk of developing post-traumatic stress disorder (PTSD). Make sure you’re getting the care you need as well. See a mental health professional if you’re experiencing depression, anxiety, and/or chronic or severe stress.

When should my child see their healthcare provider?

Your child will need regular monitoring by their healthcare team every six to 12 months (if not more often) to detect changes in cognition, movement function and behavior. If you notice new or worsening symptoms, talk to your child’s healthcare team.