Mucopolysaccharidosis Type III

It is not known why mucopolysaccharidosis type III (MPS III) mostly affects the brain. Since heparan sulfate is the sugar that is not properly broken down in MPS III, it is likely toxic to the brain. But as of January 2016, scientists do not know why this is.

Genes are passed down from parent to child. This means that blood relatives share many of the same genes since they share common relatives. The closer related people are, the more genes they share. For example, siblings (brothers/sisters) will share more genes than cousins, because siblings have the same parents while cousins only have the same grandparents. Since families share genes, they also share gene changes/mutations. This means that if one family member has a gene change/mutation, other family members have an increased chance of having the same change. If two people who are related by blood want to have children together, there is a higher chance that they will both be carriers for the same condition, like MPS III, than if they had children with someone who is not related and does not share their genes.

To learn more about inheritance, contact a genetic counselor. A genetic counselor in the area can be found on the National Society of Genetic Counselor’s “Find a Genetic Counselor” page

Because mucopolysaccharidosis type III (MPS III) is a genetic condition, the gene changes/mutations that cause it can be passed down from one family member to the next. Each type of mucopolysaccharidosis type III (MPS III) is caused by a change/mutation in a different gene:

From studying people who have mucopolysaccharidosis type III (MPS III), it appears that MPS IIIA is the most severe type. People with MPS IIIA seem to have more severe symptoms that progress faster (worsen with time). They also have a shorter life expectancy than people with types B, C, or D.

From studying people around the world with mucopolysaccharidosis type III (MPS III), it seems like MPS IIIA is most common in general. However, in certain populations, other types of MPS III are more common.

The National MPS Society keeps a list of parents who have agreed to be contacted by other families affected by Mucopolysaccharidosis type III at http://mpssociety.org/support/ask-the-parents/. They also have other support resources that may help you get in touch with other families at http://mpssociety.org/mps/mps-iii/.

Most people with mucopolysaccharidosis type III (MPS III) start showing symptoms of the condition between the ages of 2 and 6 years old.

The pediatrician should be notified if a child begins to show any signs or symptoms associated with MPS III.

Patients with Mucopolysaccharidosis type III (MPS III) will need a team of health care professionals to help manage and treat their condition. Some of these health care professionals the patient may need include:

Mucopolysaccharidosis type III is usually abbreviated to MPS III. The four types of MPS III are given a letter (A, B, C, or D) that is added on the end to indicate which type a person has: MPS IIIA, MPS IIIB, MPS IIIC, or MPS IIID.

The best person to figure out if someone may have MPS III is a geneticist (doctor with special training in genetics), or other doctor with special training and experience in MPS disorders. You can ask your primary doctor for a referral or recommendation. The American College of Medical Genetics and Genomics (ACMG) also has a "Find a Genetics Clinic" search function that can help you find a genetics specialist near you. ACMG Find a Genetic Service

Mucopolysaccharidosis type III (MPS III) affects all organs in a person’s body. This means that as the disease progresses, all the organs have more and more trouble doing their normal jobs in the body. The most common cause of death for people with MPS III is pneumonia because their bodies are not strong enough to fight off infection.

Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a genetic condition in which a person is unable to break down large sugar molecules known as a glycosaminoglycans (GAGs). In MPS III, a specific GAG called heparan sulfate is unable to be broken down and builds up over time. Patients with MPS III usually appear normal at birth. Children may meet milestones up until age 2-6 and then start showing abnormal behaviors that get worse as the child gets older. At approximately 3-5 years of age most patients begin to develop mental and motor developmental delay, resulting in mental retardation. By age 10 other symptoms appear including wobbly and erratic gait and difficulty walking, aggressive behavior, stiff joints, skeletal abnormalities, hernias, enlarged liver and/or spleen (hepatosplenomegaly), hyperactivity, seizures, deafness, loss of vision, progressive dementia, and an inability to sleep for more than a few hours at a time. Most people with MPS III may survive into their teenage years, though some can survive into their twenties.

There are four different subtypes of MPS III, caused by changes/mutations in one of four different genes:

The following is a list of health problems that can occur in a person with mucopolysaccharidosis type III:

Each type of mucopolysaccharidosis type III (MPS III) is caused by a change/mutation in a different gene:

"Characteristic facial features" means that people with mucopolysaccharidosis type III (MPS III) share some parts of their appearance. It does not mean that there is anything wrong with their faces or that they have a deformity or problem with their faces. Typically, people with MPS III have what is known as "coarse facial features" which are a unique group of features that present together and include full lips, large rounded cheeks, broad nose, and a large tongue.

If you think of a person’s genetic information like a set of instructions, everyone has spelling differences in their genes (e.g. theater vs. theatre). That’s what makes us all different! A "variant" is a genetic spelling difference that has never been seen before or is not understood very well. If you have inherited a "variant" in a gene that causes mucopolysaccharidosis type III (MPS III), it means that there is a difference in how your gene is spelled, but that we don’t yet know if this difference has any affect on the enzyme that it’s supposed to make, or if it is just the way your gene is normally spelled with no affect on the enzyme. These variant results can also be called "variants of uncertain significance" or "variants of unknown significance". If we know the spelling difference makes the gene work less or not at all, it is called a mutation.

Since MPS III is caused by spelling changes in both of a person’s copies of a gene, it is possible to see someone who has one variant and one known mutation, or even someone with 2 variants. If this person is having symptoms of MPS III, it makes it more likely that the variants are spelling errors that make the gene work less well. If they are not having symptoms, it makes it more likely that this is just a normal spelling difference that does not affect how well the gene works.

If you’ve been told that you or a family member has a "variant" in a gene that is related to MPS III, a genetic counselor may help you better understand what that means. A genetic counselor in the area can be found on the National Society of Genetic Counselor’s “Find a Genetic Counselor” page of the website: NSGC Find a Genetic Counselor

Patients with MPS III usually appear normal at birth. Children may meet milestones up until age 2-6 and then start showing abnormal behaviors that get worse as the child gets older. At approximately 3-5 years of age most patients begin to develop mental and motor developmental delay, resulting in mental retardation. By age 10 other symptoms appear including wobbly and erratic gait and difficulty walking, aggressive behavior, stiff joints, hernias, enlarged liver and/or spleen (hepatosplenomegaly), hyperactivity, seizures, deafness, loss of vision, progressive dementia, and an inability to sleep for more than a few hours at a time. The average lifespan of a person with MPS III is into their teens to twenties.

For a more complete list of symptoms that can be associated with each subtype of MPS III, check out the following links:

Behavioral changes are usually the first sign of mucopolysaccharidosis type III (MPS III). These changes can be things like very obvious over active or destructive behaviors. Children may be restless and have trouble sleeping. These changes are usually first noticed in children between the ages of 4 and 6 years old.

If you notice any of theses behavioral changes in your child, notify your child’s pediatrician.

The penetrance of mucopolysaccharidosis type III (MPS III) is complete. This means that everyone who does not have a working copy of any of the 4 genes (SGSH, NAGLU, HGSNAT, and GNS) that cause MPS III will have some symptoms of the condition. However, the expression of MPS III is variable. This means that different people with MPS III can have different symptoms from each other. Expression of the disease depends on the gene involved and the type of change/mutation in that gene.

There is prenatal testing available for mucopolysaccharidosis type III (MPS III). Prenatal testing can be done in pregnancies that are at an increased risk of having MPS III, usually because both parents are carriers. It is essential that the type of MPS III (A, B, C, or D) in the family is known before doing prenatal testing because each type requires a different test. This testing can be done in 2 ways:
1) Genetic testing of the baby to see if they have the same changes/mutations in a gene causing MPS III as their parents
2) Enzyme function testing to see if the enzymes that can cause MPS III are working properly or not

Newborn screening is a state run program that screens babies at birth for certain serious medical conditions. As of January 2016, Mucopolysaccharidosis Type II (MPS II) is not included on the newborn screen testing.

To learn more about newborn screening in a specific state, go to Baby’s First Test

There are many clinical research studies going on for mucopolysaccharidosis type III as of February 2016. These studies are investigating things like new treatments, gene therapy, and progression/features of the disease.

There are a few places you can start if you are looking for clinical research trials on mucopolysaccharidosis type III (MPS III):

As of January 2016, there is no cure for mucopolysaccharidosis type III. When treating children with mucopolysaccharidosis type III (MPS III), the goal is to improve their quality of life and slow down the progression of the disease as much as possible. Current treatments are therefore aimed at each specific symptom.

A geneticist (doctor with special training in genetics), or other doctor with special training and experience in lysosomal storage disorders and MPS can help coordinate the care for a patient with MPS III. Often these doctors also work closely with genetic counselors who can provide patients with support and referrals. You can ask your primary doctor for a referral or recommendation. The American College of Medical Genetics and Genomics (ACMG) also has a "Find a Genetics Clinic" search function that can help you find a genetics specialist near you. ACMG Find a Genetic Service

A person with a change or mutation in both copies of one of the four genes associated with mucopolysaccharidosis type III (MPS III) (SGSH, NAGLU, HGSNAT, and GNS) will be affected with MPS III.

Mucopolysaccharidosis type III (MPS III) is a lysosomal storage disorder (LSD). The body is made up of trillions of cells. Each cell has different parts that help the body to function correctly. One of the parts of the cell is called the lysosome. Lysosomes are the "garbage disposal" of the cell. They break down and recycle things called molecules (sugars, proteins, etc.) that the cell no longer needs. If someone has an LSD, their cells cannot break these things down because they are either missing a specific enzyme, a specific enzyme is not being made in enough quantity, or a specific enzyme is not being made properly. As a result there is build up in the cells of the waste molecules. Over time this build up causes the cells to stop working properly and a person with an LSD can start showing symptoms of the disease.

Mucopolysaccharidosis type III is a type of lysosomal storage disorder (LSD) that causes problems with the brain and spinal cord. It is different from other lysosomal storage disorders because there are fewer physical symptoms than in other LSDs.

The best person to figure out if someone has mucopolysaccharidosis type III (MPS III) is a geneticist or someone who specializes in lysosomal storage disorders. You can ask your primary doctor for a referral or recommendation. The American College of Medical Genetics and Genomics (ACMG) also has a "Find a Genetics Clinic" search function that can help you find a genetics specialist near you. ACMG Find a Genetic Service

While the urine and blood tests to diagnose mucopolysaccharidosis type III (MPS III) are pretty simple, it can be hard for a doctor to realize when they need to test for MPS III. This is because MPS III causes relatively mild physical symptoms. Kids with MPS III don’t have as obvious facial features, large organs, or bone problems as kids with other related genetic diseases. Most of the symptoms of MPS III are in the brain, like developmental delays and behavioral problems, which are common symptoms in a lot of children and can be caused by a lot of reasons. If you suspect your child has MPS III, ask your doctor to do urine tests for heparan sulfate and blood tests for the enzymes involved in MPS III. The earlier a child gets a diagnosis of MPS III the better!

While it is not impossible for this to happen, it would be very rare! Each type of MPS III is caused by changes/mutations in a different gene. If you have a child with one type of MPS III, like MPS IIIA, it means that both of the child’s parents are carriers for a change/mutation in the gene that causes that specific type. For another child to be born from the same parents to have a different type of MPS III, the parents would have to also be carriers for a change/mutation in the gene that causes that type! The chances of this happening are very small.

To learn more, contact a genetic counselor. A genetic counselor in the area can be found on the National Society of Genetic Counselor’s “Find a Genetic Counselor” page

Since mucopolysaccharidosis type III (MPS III) is inherited in an autosomal recessive manner, which means your child had to have inherited a change/mutation in both copies of the gene causing MPS III. That is, both mom’s copy and dad’s copy of the gene have a change/mutation. Therefore, both parents of the child are carriers for MPS III.

To learn more about inheritance, contact a genetic counselor. A genetic counselor in the area can be found on the National Society of Genetic Counselor’s “Find a Genetic Counselor” page

No, if you are both carriers for a different type of MPS III, your children are not at an increased risk of having MPS III. Each type of mucopolysaccharidosis type III (MPS III) is caused by a change/mutation in a different gene:

Each type of mucopolysaccharidosis type III (MPS III) is caused by a change/mutation in a different gene:

Many of the support organizations for Lysosomal Storage Diseases take donations to help fund clinical research on conditions like mucopolysaccharidosis type III. Visit the website of you support organization of choice to find out how you can donate:

Testing for mucopolysaccharidosis type III (MPS III) may be done in people with symptoms of the condition who also have high levels of heparan sulfate (type of sugar) in their urine. In MPS III, heparan sulfate builds up inside cells due to a problem with one of four enzymes (depending on the type of MPS III) that are supposed to break down this sugar.
One way to get tested for MPS III is for your doctor to look at the levels of the enzymes that cause MPS III in your blood. This will allow them to see if any of these enzyme levels are lower than they should be. If an enzyme level is low, they can tell which type (MPS III A, B, C, or D) you have. After the enzyme test, genetic testing may be done to find the specific gene change/mutation causing MPS III and can help to confirm the diagnosis in the person. While genetic testing is not required to diagnose MPS III (since enzyme testing can do that by itself), genetic testing can help other family members get tested for the specific gene change that is running in the family.

It may be helpful to talk to a genetic counselor to help figure out who in a family should be tested and what type of testing should be done. Go to National Society of Genetic Counselor’s “Find a Genetic Counselor” page of the website NSGC Find a Genetic Counselorto find a genetic counselor in your area.

There are many hospitals across the United States that have Lysosomal Storage Disease Centers. These centers are specialized to help diagnose, manage, and treat patients with lysosomal storage diseases like mucopolysaccharidosis type III. The National MPS Society has an extensive list of hospitals across the US who have MPS Genetics Centers (http://mpssociety.org/treatments/resources/).

It is estimated that about 1 in 70,000 people are born with any type of mucopolysaccharidosis type III (MPS III). It is the most common type of the seven mucopolysaccharide disorders.

When the type of gene change/mutation directly impacts the symptoms of the disease, it is called a "genotype-phenotype" correlation. There are some genotype-phenotype correlations known to occur in mucopolysaccharidosis type IIIA (MPS IIIA). In MPS IIIA, symptoms are usually well-correlated with the specific gene changes/mutations in the SGSH gene . There are known gene changes that seem to always cause less severe symptoms and others that always cause more severe symptoms. For more information about the genotype-phenotype correlation of each subtype of MPS III, check out the links for each subtype:

For the genetic testing, blood and saliva samples can be tested. A biopsy is not necessary for genetic testing purposes.

While there are no environmental factors or activities that can make the symptoms of mucopolysaccharidosis type III (MPS III) develop faster or become more severe, breathing problems associated with MPS III can get worse if an affected person is given general anesthesia.

In general, the physical symptoms of mucopolysaccharidosis type III (MPS III) are mild. People with MPS III will grow to a pretty normal height. Typically, people with MPS III have what is known as "coarse facial features" which are a unique group of features that present together and include full lips, large rounded cheeks, broad nose, and a large tongue. The coarse facial features may appear, but are usually usually mild. Children with MPS III tend to have thick hair, more hair on the body, and bushy eyebrows.

For mucopolysaccharidosis type IIIA (MPS IIIA) and MPS IIIC, studies have shown that carriers can be found by testing enzyme function.

Usually, children with mucopolysaccharidosis type III (MPS III) learn to speak when they are young, though it might happen later than other children who don’t have MPS III. Unfortunately, since MPS III is a progressive disorder, these children will eventually lose their ability to speak and to understand speech.

Some children with mucopolysaccharidosis type III (MPS III) can be toilet trained, though it might happen later than other children who don’t have MPS III. Other children with MPS III may never learn to use the toilet on their own. Since MPS III is a progressive disorder, children who are toilet trained will eventually lose this ability.

Mucopolysaccharidosis type III (MPS III) is also known as Sanfilippo syndrome. Since there are multiple genes that can cause MPS III, there are different names for each subtype. Each subtype results in a change in an enzyme that is needed to break down heparan sulfate.

There are many good support groups and organizations out there for people with mucopolysaccharidosis type III (MPS III). Depending on where you live, one of the following national resources may be helpful for you:

All forms of mucopolysaccharidosis type III are genetic. Each type of mucopolysaccharidosis type III (MPS III) is caused by a change/mutation in a different gene:

There are a few genetic tests that a doctor might order to test for mucopolysaccharidosis type III (MPS III) because there are different types of changes/mutations in the four genes that can cause MPS III. Each type of mucopolysaccharidosis type III (MPS III) is caused by a change/mutation in a different gene:

Other types of mucopolysaccharidoses (e.g. MPS I, MPS II) have some similarities to MPS III. Multiple sulfatase deficiency, and mucolipidosis type II, and mucolipidosis type III also share many of the same symptoms as MPS III.

The best person to figure out if someone may have MPS III is a geneticist (doctor with special training in genetics), or other doctor with special training and experience in lysosomal storage disorders and MPS. You can ask your primary doctor for a referral or recommendation. The American College of Medical Genetics and Genomics (ACMG) also has a "Find a Genetics Clinic" search function that can help you find a genetics specialist near you. ACMG Find a Genetic Service

Stem cell transplants (from healthy umbilical cord cells) to help restore the activity of the deficient enzyme are being studied to see if they can help children with MPS III, but there is no long-term data on this method of treatment yet. Studies with stem cells transplants from bone marrow were found not to be helpful. Enzyme replacement therapy, which is used to treat other kinds of MPS, is not helpful in MPS III since enzymes cannot cross the blood-brain-barrier. Since most of the symptoms of MPS III are in the brain, this is where the enzyme is needed most.