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Disease Information

Summary

Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a disorder that primarily affects the brain and spinal cord (central nervous system). It is characterized by deterioration of neurological function (neurodegeneration), resulting in many of the features of the condition. Other body systems can also be involved, although the physical features are usually mild in the early stages. People with MPS III generally do not display any features of the condition at birth, but they begin to show signs and symptoms of the disorder during early childhood. Early signs and symptoms of MPS III can include frequent ear and throat infections or bowel problems, though most common are mild developmental delay or delayed speech. Behavioral problems often worsen with affected children becoming restless, hyperactive, destructive, anxious, impulsive, fearless, or aggressive. Some affected children display features of autism spectrum disorder, which is a condition characterized by difficulty with social interactions and communication. Children with MPS III may have an increased tendency to chew on objects or put things in their mouth (be hyperoral). Sleep disturbances are also very common in children with MPS III. This condition causes progressive intellectual disability and the loss of previously acquired skills (developmental regression or dementia). In later stages of the disorder, people with MPS III may develop seizures, loss of mobility, and movement disorders. The physical features of MPS III are less pronounced than those of other types of mucopolysaccharidosis. Individuals with MPS III typically have mildly 'coarse' facial features, a prominent forehead, a large head (macrocephaly), and thick hair and eyebrows. Some people with MPS III have short stature, joint stiffness, or mild dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray.  People with MPS III often have a slightly enlarged liver (mild hepatomegaly) or spleen (mild splenomegaly), and a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). Cardiac abnormalities may also occur in this condition, including weakening of the heart muscle (cardiomyopathy), disruption of the heart's normal rhythm (arrhythmia), or problems with the heart's valves. Affected individuals often experience chronic diarrhea and recurrent upper respiratory and ear infections. People with MPS III may also have hearing loss and vision problems. MPS III is divided into types IIIA, IIIB, IIIC, and IIID, which are distinguished by their genetic cause. The different types of MPS III have similar signs and symptoms, although the features of MPS IIIA typically appear earlier in life and progress more rapidly. People with MPS III usually live into adolescence or early to mid-adulthood.

About Sanfilippo syndrome

Many rare diseases have limited information. Currently, GARD aims to provide the following information for this disease:

  • Symptoms:May start to appear as a Child.
  • Cause:This disease has more than one possible cause.
  • Organizations:Patient organizations dedicated to this rare disease are available on GARD, or you may contact a GARD Information Specialist for additional information.
  • Categories:Genetic diseases(Genetic diseases affect the DNA, or genetic instructions, which directs how tissues, organs, and body systems function.)Neurological diseases(Neurological diseases affect the brain, spinal cord, cranial nerves, autonomic nerves, or other peripheral nerves.)Inherited Metabolic diseases(Inherited metabolic diseases, or inborn errors of metabolism, are a group of genetic diseases that affect the ability of the body's cells to convert food into energy.)Birth defects(Birth defects are structural changes present at birth that can affect almost any part of the body, including how the body looks, works, or both.)Lysosomal Storage diseases(Lysosomal storage diseases are a group of genetic metabolic diseases that affect the ability of the body's cells to break down substances and remove toxins.)

Resource(s) for Medical Professionals and Scientists on This Disease:

  • GeneReview provides clinical information on genetic diseases, including diagnosis, treatment, and genetic counseling.
  • MONDO provides GARD with information for this disease.
  • Orphanet provides GARD with information for this disease.

Resource(s) for Medical Professionals and Scientists on This Disease:

  • GeneReview provides clinical information on genetic diseases, including diagnosis, treatment, and genetic counseling.
  • MONDO provides GARD with information for this disease.
  • Orphanet provides GARD with information for this disease.

About Sanfilippo syndrome

Many rare diseases have limited information. Currently, GARD aims to provide the following information for this disease:

  • Symptoms:May start to appear as a Child.
  • Cause:This disease has more than one possible cause.
  • Organizations:Patient organizations dedicated to this rare disease are available on GARD, or you may contact a GARD Information Specialist for additional information.
  • Categories:Genetic diseases(Genetic diseases affect the DNA, or genetic instructions, which directs how tissues, organs, and body systems function.)Neurological diseases(Neurological diseases affect the brain, spinal cord, cranial nerves, autonomic nerves, or other peripheral nerves.)Inherited Metabolic diseases(Inherited metabolic diseases, or inborn errors of metabolism, are a group of genetic diseases that affect the ability of the body's cells to convert food into energy.)Birth defects(Birth defects are structural changes present at birth that can affect almost any part of the body, including how the body looks, works, or both.)Lysosomal Storage diseases(Lysosomal storage diseases are a group of genetic metabolic diseases that affect the ability of the body's cells to break down substances and remove toxins.)

Causes

What Causes This Disease?

Genetic Mutations

Changes in your genes (also called variants) cause Sanfilippo syndrome.

Genes are sections of DNA that contains instructions that help the body grow, develop, and function. A genetic variant is a change in your DNA's order. Parents may pass variants to their children, or they may occur randomly. They may result from viruses, environmental factors, such as UV radiation, or a combination of causes.

Most genetic variants do not cause disease. However, some can affect how a gene works and interfere with the body's normal functions. A pathogenic variant is one that causes disease.

If you think you may have this disease, collect your family health history (CDC). It may help you and your medical team to know about family members who have had the disease or similar symptoms and when those symptoms first appeared.

Read more about genetic disorders (NIH MedlinePlus). 

Genetic Mutations

Changes in your genes (also called variants) cause Sanfilippo syndrome.

Genes are sections of DNA that contains instructions that help the body grow, develop, and function. A genetic variant is a change in your DNA's order. Parents may pass variants to their children, or they may occur randomly. They may result from viruses, environmental factors, such as UV radiation, or a combination of causes.

Most genetic variants do not cause disease. However, some can affect how a gene works and interfere with the body's normal functions. A pathogenic variant is one that causes disease.

If you think you may have this disease, collect your family health history (CDC). It may help you and your medical team to know about family members who have had the disease or similar symptoms and when those symptoms first appeared.

Read more about genetic disorders (NIH MedlinePlus). 

What causes disruption in metabolism?

Sanfilippo syndrome is caused by a disruption in a person's metabolism. Metabolism is the series of chemical reactions in our body that turns the food we eat into energy and removes toxins. Hormones and specific proteins, called enzymes, help make the right chemical reactions happen in the right order. However, genetic changes can prevent hormones or enzymes from working properly, which can lead to a disruption in metabolism such as energy not being created for the body or toxins not being removed from the body. Learn more about inherited metabolic diseases from the National Human Genome Research Institute (NHGRI).

Impaired Lysosomal Function

This disease is caused by an impairment, or issue, in lysosomal function. Lysosomes are located inside cells and contain digestive enzymes that help break down fats, sugars, and other substances to create energy for the body. Genetic mutations can affect lysosomes such as having a missing or non-functioning digestive enzyme. This can prevent cells from properly breaking down toxins or moving them out of the cell. If toxins build up, the cell may become damaged or die. Depending on their location in the body, these damaged or dead cells may affect different organs and body systems.

Can diseases be passed down from parent to child?

A biological parent can sometimes pass down genetic changes, called mutations, that cause a disease or increase the chances of developing it. This is called inheritance. Knowing if other family members have had the disease, also known as your family health history, can give your medical team important information. The Surgeon General offers a tool to help you collect your family health history.

Autosomal Recessive

Autosomal means the gene involved is located on one of the numbered chromosomes. Recessive means that a child must inherit two copies of the mutated gene, one from each biological parent, to be affected by the disease. A carrier is a person who only has one copy of the genetic mutation. A carrier usually doesn't show any symptoms of the disease.

If both biological parents are carriers, there is a 25% their child inherits both copies of the mutated gene and is affected by the disease. Additionally, there is a 50% chance their child inherits only one copy of the mutated gene and is a carrier.

Learn more about inheritance patterns from the National Library of Medicine (NLM).

Autosomal Recessive

Autosomal means the gene involved is located on one of the numbered chromosomes. Recessive means that a child must inherit two copies of the mutated gene, one from each biological parent, to be affected by the disease. A carrier is a person who only has one copy of the genetic mutation. A carrier usually doesn't show any symptoms of the disease.

If both biological parents are carriers, there is a 25% their child inherits both copies of the mutated gene and is affected by the disease. Additionally, there is a 50% chance their child inherits only one copy of the mutated gene and is a carrier.

Learn more about inheritance patterns from the National Library of Medicine (NLM).

When Do Symptoms of Sanfilippo syndrome Begin?

Symptoms of this disease may start to appear as a Child.

The age symptoms may begin to appear differs between diseases. Symptoms may begin in a single age range, or during several age ranges. The symptoms of some diseases may begin at any age. Knowing when symptoms may have appeared can help medical providers find the correct diagnosis.
  1. Prenatal
    Before Birth
  2. Newborn
    Birth-4 weeks
  3. Infant
    1-23 months
  4. Child Selected
    2-11 years
  5. Adolescent
    12-18 years
  6. Adult
    19-65 years
  7. Older Adult
    65+ years
Symptoms may start to appear as a Child.
This information comes from Orphanet

Symptoms

You may have one or more symptoms, and they may be mild or severe. Having some or all of these symptoms does not mean you have this disease. Only a health care provider can diagnose you.

Common

Many people have these, but not everyone.

  • Abnormal collarbone (Abnormal clavicle morphology)
  • Abnormal facial shape
  • Abnormal form of the vertebral bodies
  • Abnormal gait (Gait disturbance)
  • Abnormality of the ribs (Abnormal rib morphology)
  • Abnormally shaped skeletal (Abnormal skeletal morphology)
  • Adenoiditis
  • Ataxia
  • Behavioral abnormality (Atypical behavior)
  • Brain imaging abnormality
  • Central nervous system degeneration
  • Chronic infections of the middle ear (Chronic otitis media)
  • Close sighted (Myopia)
  • Clouding of the lens of the eye (Cataract)
  • Coarse facial features
  • Coarse hair
  • Delayed speech and language development
  • Difficulty sleeping (Sleep disturbance)
  • Early and severe mental retardation (Severe intellectual disability)
  • Enlarged liver (Hepatomegaly)
  • Excessive bone growth of the skull and face (Craniofacial hyperostosis)
  • Excessive hairiness (Hirsutism)
  • Excessive hairiness over body (Generalized hirsutism)
  • Hearing impairment
  • Hypertonia
  • Increased spleen size (Splenomegaly)
  • Intermittent diarrhea
  • Knock knees (Genu valgum)
  • Loss of developmental milestones (Developmental regression)
  • Malabsorption
  • Middle ear infection (Otitis media)
  • Monobrow (Synophrys)
  • More active than typical (Hyperactivity)
  • Recurrent inflammation of tonsils (Recurrent tonsillitis)
  • Recurrent sinus and lung infections (Recurrent sinopulmonary infections)
  • Respiratory tract infection
  • Specific learning disability
  • Thick hair
  • Weakness of the vocal cords (Vocal cord paresis)
  • Worsening neurological symptoms (Progressive neurologic deterioration)

Uncommon

Some people have these, but most people do not.

  • Abnormal aortic valve morphology
  • Abnormal dentition (Abnormality of the dentition)
  • Abnormal mitral valve morphology
  • Abnormal myocardium morphology
  • Abnormal pyramidal sign
  • Abnormal temper tantrums
  • Abnormality of the middle ear ossicles
  • Abnormally large tongue (Macroglossia)
  • Aggressive behavior
  • Amplification of sexual behavior
  • Aspiration pneumonia
  • Avascular necrosis of the capital femoral epiphysis
  • Belly sticks out (Protuberant abdomen)
  • Blindness
  • Conductive deafness (Conductive hearing impairment)
  • Constipation
  • Constrictive median neuropathy
  • Corneal opacity
  • Dementia
  • Difficulty articulating speech (Dysarthria)
  • Disinhibition
  • Dysostosis multiplex
  • Enlarged heart (Cardiomegaly)
  • Fatigable weakness of swallowing muscles
  • Flexed joint that cannot be straightened (Flexion contracture)
  • Full lips (Thick vermilion border)
  • Hip dysplasia
  • Hip pain
  • Hyperactive deep tendon reflexes
  • Hyperorality
  • Increased size of skull (Macrocephaly)
  • Increased susceptibility to fractures
  • Inguinal hernia
  • Intellectual disability
  • Interruption of electrical communication between upper and lower chambers of heart (Atrioventricular block)
  • Involuntary muscle stiffness, contraction, or spasm (Spasticity)
  • Joint stiffness
  • Limited peripheral vision (Constriction of peripheral visual field)
  • Long, narrow head (Dolichocephaly)
  • Loss of ability to walk (Loss of ambulation)
  • Low solidness and mass of the bones (Reduced bone mineral density)
  • Mixed hearing impairment
  • Motor delay
  • Night blindness (Nyctalopia)
  • Obstructive sleep apnea
  • Opacification of the corneal stroma
  • Optic atrophy
  • Pigmentary retinopathy
  • Poor swallowing (Dysphagia)
  • Retina degeneration (Retinal degeneration)
  • Rod-cone dystrophy
  • Scoliosis
  • Seizure
  • Sensorineural hearing impairment
  • Thick nasal alae
  • Thickened helices
  • Too much cerebrospinal fluid in the brain (Hydrocephalus)
  • Umbilical hernia
  • Upper airway obstruction
  • Ventriculomegaly
This information comes from the Human Phenotype Ontology (HPO)

Navigating Health Care Decisions

On average, it can take more than six years to receive an accurate diagnosis. Many primary care providers (PCPs) may not be familiar with rare diseases, and patients often need to visit multiple specialists or seek second opinions to get answers.

If a diagnosis remains unclear, visiting a multidisciplinary care center or university hospital may help. These centers bring together teams of specialists who can work together to evaluate symptoms and coordinate a diagnosis. This team-based approach is also helpful after a diagnosis, when managing care for rare diseases.

Because only about 5% of rare diseases have FDA-approved treatments, finding the right healthcare team to manage your symptoms and overall health is essential. People living with rare diseases often face challenges such as delayed diagnosis, limited treatment options, and difficulty accessing knowledgeable providers. Building a care team that understands your needs can make a significant difference in your quality of life.

Your Health Care Team

Why is building the right health care team important?

Building the right health care team is key to the diagnosis, treatment, and management of your long-term health journey living with a rare disease. Start by choosing a primary care provider (PCP). Your PCP will be your main point of contact and help coordinate care with other medical professionals. Your PCP may order tests or refer you to specialists. To find a PCP near you, use the Medicare provider search tool and enter your location and “Primary Care Provider.”

Seeing multiple specialists is important for people with rare diseases because these conditions often affect many parts of the body and require care from doctors with different expertise. Most primary care providers may not be familiar with rare diseases, so involving specialists can lead to a more accurate diagnosis and better care. A coordinated team approach ensures that all symptoms are addressed and that care is well-managed. It can also connect patients with the latest research or treatment options.

A PCP that specializes in the care of children is called a pediatrician. Use this tool by the American Academy of Pediatrics to find a pediatrician in your area by inputting your location.

These specialists may help in the diagnosis, management, and treatment of Sanfilippo syndrome:

Anterior segment specialists are eye doctors with advanced training in diseases that affect the front part of the eye, such as the cornea, iris, and lens. They manage a variety of eye diseases, from common issues like cataracts to complex, rare, or genetic diseases that involve the anterior segment. Anterior segment specialists may perform surgeries or other treatments to improve vision and eye health.

You may want to consider bringing a copy of your medical history and a list of any medications to your appointment.

Use this directory by the American Academy of Ophthalmology to search for an anterior segment specialist in your area. Use the dropdown menu to select "Cataract/Anterior Segment". 
Orthopedists, also known as orthopedic surgeons, are doctors with specialized training in diagnosing and treating conditions that affect the bones, joints, muscles, tendons, and ligaments. They care for people with arthritis, scoliosis, sports injuries, bone fractures, and rare or inherited bone conditions. Orthopedists may use imaging tests and physical exams to identify the cause of pain, stiffness, or limited movement. Treatment may include physical therapy, medication, or surgery.

You may want to consider bringing a copy of your medical history and a list of any medications to your appointment.

Ask your primary care provider for a referral or use this directory by Medicare to search for an orthopedist specialist in your area. Search using the keyword “Orthopedics.”
Neurologists are doctors with specialized training in diagnosing and treating conditions that affect the brain, spinal cord, and nerves. These parts of the nervous system help control how the body moves, feels, and thinks. Neurologists often care for people with seizures, memory problems, muscle weakness, movement disorders, and inherited conditions such as muscular dystrophies. To better understand a person's symptoms, neurologists may use imaging tests that show the brain or spine, or tests that measure the brain’s electrical activity.

You may want to consider bringing a copy of your medical history and a list of any medications to your appointment.

Ask your primary care provider for a referral or use this directory provided by the American Board of Psychiatry and Neurology to find a specialist. 
Ophthalmologists are doctors with specialized training in managing serious eye problems, including those that require surgery. They may have additional experience with rare or inherited eye diseases, birth defects, or eye conditions linked to the nervous or immune system. Some ophthalmologists focus on specific areas, such as diseases of the retina or cancers of the eye. They may use imaging, vision tests, and lab work to diagnose and guide treatment.

You may want to consider bringing a copy of your medical history and a list of any medications to your appointment.

Ask your primary care provider for a referral or use this directory provided by the American Academy of Ophthalmology to find a specialist.
Geneticists are doctors trained to diagnose and manage conditions caused by genetic changes, birth defects, or metabolic disorders. Metabolic disorders affect how the body makes or uses energy. Geneticists often work alongside genetic counselors to review family history, discuss genetic risks, explain testing options, and interpret genetic test results. They help people understand how inherited conditions may affect them and their families.

You may want to consider bringing a copy of your medical history and a list of any medications to your appointment.

Ask your primary care provider for a referral or use this directory provided by the American College of Medical Genetics and Genomics to find a specialist.
Epileptologists are neurologists with advanced training in diagnosing and treating epilepsy and seizure disorders. They specialize in evaluating complex or drug-resistant forms of epilepsy, including rare types that may involve multiple seizure types or be linked to genetic or metabolic disorders. Epileptologists may use tools such as electroencephalogram (EEG), brain imaging, and genetic testing to help guide treatment.

You may want to consider bringing a copy of your medical history and a list of any medications to your appointment.

Ask your primary care provider for a referral or use this directory by Medicare to search for an epileptologist in your area. Search using the keyword “epilepsy."

Multidisciplinary Care Centers

Is It Time to Get a Second Opinion or Specialized Evaluation?

If you've visited your PCP, met with specialists, and undergone the recommended tests, but are still searching for a diagnosis, it may be time to visit an academic medical center or, for pediatric patients, a children's hospital. Academic medical centers and children's hospitals, often called multidisciplinary care centers, typically bring together specialists from different fields to work together on complex cases like rare diseases.

Multidisciplinary care centers may offer more coordinated care and be involved in clinical research, which may help reduce the time to diagnosis and provide access to emerging diagnostic tools. Specialists at these centers may have a deeper understanding of rare diseases and serve as a resource when you'd like a second opinion, particularly when test results or treatment plans are not delivering expected results.

Find hospitals that may partner with medical schools and programs in your area. 

Children’s hospitals and large teaching hospitals may also offer dedicated specialists and programs for pediatric patients with undiagnosed or rare diseases. These programs bring pediatric experts together in one place and may provide more coordinated care for your child.

Search for children's or university hospitals in your area.

Rare Disease Experts

How can you find a rare disease expert?

If a diagnosis, care management, or treatment plan remains unclear despite extensive efforts by your PCP and specialists, it may be time to find a rare disease expert for your disease, if available. A rare disease expert is a medical provider that has knowledge or training on specific rare disease(s), but there may only be a few experts in your state, region, or country. Rare disease experts may work at large research or teaching hospitals, sometimes called centers of excellence. Centers of Excellence commit to sharing knowledge and best practices that can lead to improved care and treatment for individuals living with a rare disease. 

You can also contact a GARD Information Specialist for help finding experts, centers of excellence, or clinics that focus on your disease.
You can ask your care providers for help finding an expert or use directory tools to search for experts near you. The following organization(s) may maintain a list of experts or expert centers for people living with Sanfilippo syndrome:

Find Your Community

How can patient organizations help?

Patient organizations can help patients and families connect. They build public awareness of the disease and are a driving force behind research to improve patients' lives. They may offer online and in-person resources to help people live well with their disease. Many collaborate with medical experts and researchers.

Services of patient organizations differ, but may include:

  • Ways to connect to others and share personal stories
  • Easy-to-read information
  • Up-to-date treatment and research information
  • Patient registries
  • Lists of specialists or specialty centers
  • Financial aid and travel resources


Please note: GARD provides organizations for informational purposes only and not as an endorsement of their services. Contact a GARD Information Specialist for more information on organizations that may be dedicated to this disease. Please contact an organization directly if you have questions about the information or resources it provides.


View GARD's criteria for including patient organizations, which can be found under the FAQs on our About GARD page. Request an update or to have your organization added to GARD. 

Patient Organizations

8 Organizations

Cure Sanfilippo Foundation

People With

Sanfilippo syndrome

Helpful Links
Country

United States

National MPS Society

People With

Sanfilippo syndrome

Country

United States

Team Sanfilippo Foundation

People With

Sanfilippo syndrome

Country

United States

World Craniofacial Foundation

People With

Craniofacial anomalies

Helpful Links
Country

United States

Children's Craniofacial Association

People With

Craniofacial anomalies

Country

United States

FACES: The National Craniofacial Association

People With

Craniofacial anomalies

Country

United States

myFace

People With

Craniofacial anomalies

Country

United States

Epilepsy Foundation

People With

Epilepsy

Helpful Links
Country

United States

OrganizationPeople WithHelpful LinksCountry
Cure Sanfilippo FoundationSanfilippo syndromeResearch RegistryUnited States
National MPS SocietySanfilippo syndromeUnited States
Team Sanfilippo FoundationSanfilippo syndromeUnited States
World Craniofacial FoundationCraniofacial anomaliesList of ExpertsUnited States
Children's Craniofacial AssociationCraniofacial anomaliesUnited States
FACES: The National Craniofacial AssociationCraniofacial anomaliesUnited States
myFaceCraniofacial anomaliesUnited States
Epilepsy FoundationEpilepsyList of Experts
Research Registry		United States

Participate in Research

Clinical studies are a part of clinical research and play an important role in medical advances for rare diseases. Through clinical studies, researchers may ultimately uncover better ways to treat, prevent, diagnose, and understand human diseases.

What Are Clinical Studies?

Clinical studies are medical research involving people as participants. There are two main types of clinical studies:

  1. Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments.
  2. Observational studies involve recording changes over time among a specific group of people in their natural settings.

Learn more about clinical trials from this National Institutes of Health webpage.

Why Participate in Clinical Studies?

People participate in clinical trials for many reasons. People with a disease may participate to receive the newest possible treatment and additional care from clinical study staff as well as to help others living with the same or a similar disease. Healthy volunteers may participate to help others and to contribute to moving science forward.

To find the right clinical study we recommend you consult your doctors, other trusted medical professionals, and patient organizations. Additionally, you can use ClinicalTrials.gov to search for clinical studies by disease, terms, or location.

What if There Are No Available Clinical Studies?

ResearchMatch helps connect people interested in research studies  with researchers from top medical centers across the United States. Anyone from the U.S. can register with this free program funded by NIH. Researchers from participating institutions use the database to search for and invite patients or healthy volunteers who meet their study criteria to participate.

Why may you want to consider joining the All of Us Research Program?

The All of Us Research Program is inviting 1 million people from all backgrounds across the U.S. to help build one of the most diverse health databases in history. Researchers will use the data to learn how our biology, lifestyle, and environment affect health. This may one day help them find ways to treat and prevent diseases.

ClinicalTrials.gov, an affiliate of NIH, provides current information on clinical research studies in the United States and abroad. Talk to a trusted doctor before choosing to participate in any clinical study. We recommend checking this site often and searching for studies with related terms/synonyms to improve results.
Search ClinicalTrials.gov for this disease.
GARDGenetic and Rare Diseases
Information Center
Contact a GARD Information Specialist if you need help finding more information on this rare disease or available clinical studies. Please note that GARD cannot enroll individuals in clinical studies.
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Sources & References

Last Updated: September 2026