What are the other Names for this Condition? (Also known as/Synonyms)
- Mucopolysaccharide Storage Disease Type III
- Sanfilippo Syndrome
What is Mucopolysaccharidosis Type III? (Definition/Background Information)
- Mucopolysaccharidosis Type III (MPS III or Sanfilippo Syndrome) is a rare, genetic metabolic condition that involves an inability of the body to breakdown glycosaminoglycans, which are long chains of sugar molecules. The condition is inherited in an autosomal recessive manner, meaning two copies (one from each parent) of the faulty gene are needed to cause signs and symptoms of the disorder
- The inheritance of certain faulty genes prevents the body from producing an enzyme that is responsible for breaking down the sugar molecules. This inability to breakdown these sugars, causes it to buildup leading to many defects. Mucopolysaccharidosis Type III is the most common type of mucopolysaccharidoses
- Since the condition is genetic, it is present at birth. Although, significant signs and symptoms of Mucopolysaccharidosis Type III are mostly seen during childhood and involve the brain and nervous system (leading to neurological signs and symptoms)
- A healthcare professional can use various diagnostic tools, such as a physical exam, electrocardiogram, urinalysis (analysis of urine), and X-rays of the affected regions, to help diagnose Mucopolysaccharidosis Type III
- There is no cure for Mucopolysaccharidosis Type III; however, the treatment provided is symptomatic. These can include organ-specific treatments involving corrective surgical procedures. However, enzyme replacement and bone marrow transplant are not reported to be very effective
- The prognosis of Mucopolysaccharidosis Type III depends upon the severity of the condition and the subtype. Children with milder signs and symptoms have a better prognosis than those with severe MPS Type III
Mucopolysaccharidosis Type III is subdivided into the following subtypes based on the different genes that are mutated:
- Mucopolysaccharidosis Type IIIA
- Mucopolysaccharidosis Type IIIB
- Mucopolysaccharidosis Type IIIC
- Mucopolysaccharidosis Type IIID
Who gets Mucopolysaccharidosis Type III? (Age and Sex Distribution)
- Mucopolysaccharidosis Type III is a rare congenital disorder that is present at birth. However, the signs and symptoms are not usually observed at birth, but during early childhood
- This inherited genetic disorder can affect males and females of different races and ethnic backgrounds
- The incidence of the condition is 1 in 70,000 newborns (with inclusion of all 4 subtypes):
- The prevalence of Mucopolysaccharidosis Type IIIA is more in North Western Europe
- The prevalence of Mucopolysaccharidosis Type IIIB is more in South Eastern Europe
- Mucopolysaccharidosis Type IIIC and Type IIID are seen worldwide
- MPS Types IIIA and IIIB are more common than MPS Types IIIC and IIID
What are the Risk Factors for Mucopolysaccharidosis Type III? (Predisposing Factors)
- A genetic predisposition due to family history increases the risk for Mucopolysaccharidosis Type III
It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one's chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.
Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.
What are the Causes of Mucopolysaccharidosis Type III? (Etiology)
- Mucopolysaccharidosis Type III is caused by inheriting faulty genes that prevents the body from producing certain enzymes. The condition is inherited in an autosomal recessive manner
- Depending on the subtype of MPS Type III, the gene and the enzyme it codes for varies:
- Mucopolysaccharidosis Type IIIA: The gene responsible for MPS IIIA is the SGSH gene, which codes for the enzyme heparan sulfamidase
- Mucopolysaccharidosis Type IIIB: The gene responsible for MPS IIIB is the NAGLU gene, which codes for the enzyme alpha-N-acetylglucosaminidase
- Mucopolysaccharidosis Type IIIC: The gene responsible for MPS IIIC is the HGSNAT gene, which codes for the enzyme alpha-glucosaminide N-acetyltransferase
- Mucopolysaccharidosis Type IIID: The gene responsible for MPS IIID is the GNS gene, which codes for the enzyme N-acetylglucosamine-6-sulfate sulfatase
- These enzymes are responsible for breaking down long chains of sugars, called glycosaminoglycans (GAGs). Due to a lack of production of the enzyme, GAG sugar molecules get abnormally accumulated in a structure called lysosome within the cells. The disorder is a kind of “lysosomal storage disease”, because the accumulation within special compartments of the cells, called lysosomes
- Lysosomes are a kind of recycling plant within the cells - they break down larger, more complex organic molecules into smaller molecules, which the cells can then reuse. When important enzymes are not functioning efficiently, the lysosomes become bloated and eventually, the cell gets ‘filled-up’ being unable to function anymore, leading to a disease state
- The complex molecules glycosaminoglycans used to be called “mucopolysaccharides”; the term “mucopolysaccharidosis” literally means an overabundance of mucopolysaccharides. Mucopolysaccharidosis Type 3 is also known as Sanfilippo Syndrome
Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).
What are the Signs and Symptoms of Mucopolysaccharidosis Type III?
Mucopolysaccharidosis Type III is a congenital disorder; however, noticeable features of the disorder are not commonly present at birth. The onset of significant signs and symptoms occur during childhood (typically between ages 3-6 years). The severity of the condition varies from one child to another and it may be mild or severe. The severity also depends upon the subtype of MPS Type III.
The signs and symptoms of Mucopolysaccharidosis Type III are generally the same for all 4 subtypes and may include:
- The functions of the brain and spinal cord are mostly affected, which leads to:
- Behavioral issues
- Delayed speech
- Anxiousness and restlessness in children
- Hyperactivity and aggression
- Lowered mental function and IQ levels, which progressively worsens
- Convulsions and movement disorders may develop over time
- Abnormally-shaped head with coarse facial features
- Disturbed sleep
- Mildly enlarged liver (hepatomegaly)
- Stunted growth
- Bone and joint abnormalities
- Respiratory infections
- Frequent ear infection, hearing difficulties
- Vision impairment
Note: MPS Type IIIA is a rapidly progressing condition. The signs and symptoms are also manifested much earlier in the affected child.
How is Mucopolysaccharidosis Type III Diagnosed?
Diagnostic tools used by a healthcare provider in the diagnosis of Mucopolysaccharidosis Type III can include:
- Physical examination and analysis of previous medical history
- Peripheral smear exam may reveal abnormal lymphocytes containing cytoplasmic inclusions
- Urine tests: Increased levels of dermatan sulfate and heparin sulfate may be seen
- Hearing tests
- Sleep studies may be performed
- X-ray of different parts of the body may reveal bony abnormalities
- MRI scan of brain to determine brain defects
- Genetic testing for changes in specific genes
- In many cases, the diagnosis is confirmed in the lab by conducting enzyme-based tests, which are performed on fibroblast cells or leukocytes
Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.
What are the possible Complications of Mucopolysaccharidosis Type III?
Complications of Mucopolysaccharidosis Type III may include:
- Inguinal hernia causing a bulge on the side of the pubic bone, abdominal weakness, numbness in the groin, groin pain especially while coughing or lifting heavy objects
- Umbilical hernia causing an usually painless, soft bulge at the navel; the bulge is more visible when the baby cries or coughs
- Vision and hearing loss
- Communication difficulties
- Short stature
- Frequent incidence of pneumonia
- Seizures, which are mostly seen when the child reaches 10 years of age
- Walking disability, decreased mobility
- Decreased life span
How is Mucopolysaccharidosis Type III Treated?
There is no cure for Mucopolysaccharidosis Type III, since it is a genetic condition. Treatment for MPS Type III is dependent on individual signs and symptoms and based on the organs that are affected. Since, this congenital condition involves various parts of the body and body systems, a team of healthcare professionals of diverse specialties are needed to manage MPS III. An individualized treatment (case-by-case approach) is provided to improve the quality of life. This is also based on the specific set of signs and symptoms and complications that develop in each child/individual.
The treatment measures may include:
- Organ-specific treatments as specified by the healthcare provider including:
- Orthopedic surgery for correcting bone and joint abnormalities
- Hernia repair for inguinal and umbilical hernia
- Corneal transplant for vision abnormalities
- Tonsillectomy for frequent ear and throat infections
- Correction of hearing defects
- For improving motor skills and mental disabilities, special therapeutic treatment (by physical and occupational therapists) and supportive care is required
- Currently, enzyme replacement therapy and bone marrow transplant have not been found to be very effective in treating MPS Type III (unlike other mucopolysaccharidosis types, where it is found to be beneficial)
- Research is being currently undertaken to treat Mucopolysaccharidosis Type III using gene therapy
How can Mucopolysaccharidosis Type III be Prevented?
- Currently, there are no specific methods or guidelines to prevent Mucopolysaccharidosis Type III, since it is a genetic condition
- Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
- If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
- Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Mucopolysaccharidosis Type III
- Regular medical screening at periodic intervals with tests, scans and physical examinations are mandatory
What is the Prognosis of Mucopolysaccharidosis Type III? (Outcomes/Resolutions)
Mucopolysaccharidosis Type III (Sanfilippo Syndrome) is a progressive disorder that has a generally poor prognosis. However, the prognosis also depends upon the severity of the signs and symptoms and the subtype of MPS Type III (whether A, B, C, or D).
- Children with MPS Type IIIA have the worst prognosis; most individuals do not survive beyond age 20 years
- Children with other subtypes ( MPS Types IIIB, IIIC, and IIID) are known to live up to age 40 years
Additional and Relevant Useful Information for Mucopolysaccharidosis Type III:
- The signs and symptoms of Mucopolysaccharidosis Type III are generally less prominent than other types of mucopolysaccharidosis
Please visit our Congenital & Genetic Disorders Health Center for more physician-approved health information: