Sanfilippo syndrome
MPS III; Sanfilippo syndrome; MPS IIIA; MPS IIIB; MPS IIIC; MPS IIID; Lysosomal storage disease - mucopolysaccharidosis type III
Mucopolysaccharidosis type III (MPS III) is a rare disease in which the body is missing or does not have enough of certain enzymes needed to break down long chains of sugar molecules. These chains of molecules are called glycosaminoglycans (formerly called mucopolysaccharides). As a result, the molecules build up in different parts of the body and cause various health problems.
The condition belongs to a group of diseases called mucopolysaccharidoses (MPSs). MPS III is also known as Sanfilippo syndrome.
There are several other types of MPSs, including:
- MPS I (Hurler syndrome; Hurler-Scheie syndrome; Scheie syndrome)
- MPS II (Hunter syndrome)
- MPS IV (Morquio syndrome)
Autosomal recessive is one of several ways that a trait, disorder, or disease can be passed down through families. An autosomal recessive disorder means two copies of an abnormal gene must be present in order for the disease or trait to develop. For a child born to a couple who both carry the gene (but the parents themselves do not have signs of disease), the expected outcome for each pregnancy is: a 50% chance that the child is born with one normal and one abnormal gene (carrier, without disease), a 25% chance that the child is born with two normal genes (normal), and a 25% chance that the child is born with two abnormal genes (at risk for the disease). Note: These outcomes do not mean that the children will definitely be carriers or be severely affected.
Causes
MPS III is an inherited disorder. This means it is typically passed down through families. If both parents carry a nonworking copy of a gene related to this condition, each of their children has a 25% (1 in 4) chance of developing the disease. This is called an autosomal recessive trait.
MPS III occurs when the enzymes needed to break down the heparan sulfate sugar chain are missing or defective.
There are four main types of MPS III. The type a person has depends on which enzyme is affected.
- Type A is caused by a defect in the SGSH gene and is the most severe form. People with this type do not have a normal form of the enzyme called heparan N-sulfatase.
- Type B is caused by a defect in the NAGLU gene. People with this type are missing or do not produce enough alpha-N-acetylglucosaminidase.
- Type C is caused by a defect in the HGSNAT gene. People with this type are missing or do not produce enough acetyl-CoA:alpha-glucosaminide N-acetyltransferase.
- Type D is caused by a defect in the GNS gene. People with this type are missing or do not produce enough N-acetylglucosamine 6-sulfatase.
Symptoms
Symptoms often appear after the first year of life. A decline in learning ability typically occurs between ages 2 and 6. The child may have normal growth during the first few years, but final height is below average. Delayed development is followed by worsening mental status.
Other symptoms may include:
- Behavioral problems, including hyperactivity
- Coarse facial features with heavy eyebrows that meet in the middle of the face above the nose
- Chronic diarrhea
- Enlarged liver and spleen
- Sleep difficulties
- Stiff joints that may not extend fully
- Vision problems and hearing loss
- Walking problems
Exams and Tests
Your health care provider will perform a physical exam.
Urine tests will be done. People with MPS III have a large amount of a mucopolysaccharide called heparan sulfate in the urine.
Other tests may include:
- Blood enzyme level
- Echocardiogram
- Genetic testing
- Slit lamp eye exam
- Skin fibroblast culture
- X-rays of the bones
Treatment
Treatment of MPS III is aimed at managing the symptoms. There is no specific treatment for this disease. New research is under development for gene therapy and enzyme replacement.
Support Groups
More information and support for people with MPS III and their families can be found at:
- National MPS Society --
mpssociety.org/ - National Organization for Rare Disorders --
rarediseases.org/rare-diseases/mucopolysaccharidosis-type-iii/ - NIH Genetic and Rare Diseases Information Center --
rarediseases.info.nih.gov/diseases/3807/mucopolysaccharidosis-type-iii - Team Sanfilippo Foundation --
teamsanfilippo.org/
Outlook (Prognosis)
MPS III causes significant nervous system symptoms, including severe intellectual disability. Most people with MPS III live into their teenage years. Some live longer, while others with severe forms die at an earlier age. Symptoms are most severe in people with type A.
Possible Complications
These complications can occur:
- Blindness
- Inability to care for self
- Intellectual disability
- Nerve damage that slowly gets worse and eventually requires wheelchair use
- Seizures
When to Contact a Medical Professional
Contact your child's provider if your child does not seem to be growing or developing normally.
See your provider if you plan to have children and you have a family history of MPS III.
Prevention
Genetic counseling is recommended for couples who want to have children and who have a family history of MPS III. Prenatal testing is available.
References
Pearse Y, Iacovino M. A cure for Sanfilippo syndrome? A summary of current therapeutic approaches and their promise. Med Res Arch. 2020;8(2):10. PMID: 32733997
Pyeritz RE. Inherited diseases of connective tissue. In: Goldman L, Cooney KA, eds. Goldman-Cecil Medicine. 27th ed. Philadelphia, PA: Elsevier; 2024:chap 239.
Spranger JW. Mucopolysaccharidoses. In: Kliegman RM, St. Geme JW, Blum NJ, Shah SS, Tasker RC, Wilson KM, eds. Nelson Textbook of Pediatrics. 21st ed. Philadelphia, PA: Elsevier; 2020:chap 107.
Turnpenny PD, Ellard S, Cleaver R. Inborn errors of metabolism. In: Turnpenny PD, Ellard S, Cleaver R, eds. Emery's Elements of Medical Genetics and Genomics. 16th ed. Philadelphia, PA: Elsevier; 2022:chap 18.
Version Info
Last reviewed on: 4/24/2023
Reviewed by: Anna C. Edens Hurst, MD, MS, Associate Professor in Medical Genetics, The University of Alabama at Birmingham, Birmingham, AL. Review provided by VeriMed Healthcare Network. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.
