Mucopolysaccharidosis Type I

Overview

What is Hurler syndrome?

Mucopolysaccharidosis type I (MPS I) is a progressive genetic disease that occurs when the level of an enzyme in the body, the alpha-L-iduronidase enzyme, is too low for it to do its job correctly (or absent completely). Alpha-L-iduronidase is involved in the breakdown of certain complex sugars in the body. These complex sugars are different from what we eat in our diet, and are called glycosaminoglycans (GAGs). Because the alpha-L-iduronidase enzyme level is too low, the GAGs called dermatan sulfate and heparan sulfate are not broken down and become stored in the lysosomes of the cells. Cells make up our entire body and all the tissues of our body; we have skin cells, heart cells, blood cells, etc. Lysosomes are the "recycling centers" located in the cells of our body, and this is where the alpha-L-iduronidase enzyme is found. When it is not working correctly, dermatan sulfate and heparan sulfate are not broken down and become stored in (clog up) the lysosomes. The lysosomes grow larger and larger as the storage continues. Eventually, the cell can no longer work properly because of the enlarged lysosomes. This causes tissue and organ damage, resulting in the symptoms seen in MPS I. Common symptoms are hernias in the belly button and/or groin, skeletal problems (including some abnormal bone development), recurrent upper respiratory tract infections, hydrocephalus (extra fluid on the brain), sleep apnea (pausing of breathing during sleep), hearing loss, enlarged liver and spleen, corneal clouding (a "haze" in the colored portion of the eyes), and heart valve problems. People with MPS I often look different from their family members. Their facial features are usually "coarse," meaning they have thick eyebrows, thick lips, widely spaced teeth, and a flat nasal bridge with a button nose.

Mucopolysaccharidosis type I (MPS I) is inherited in an autosomal recessive pattern through families. The word autosome means that a specific gene associated with a disease or condition is located on one of the numbered, non-sex chromosomes (packaged and thread-like looking structures in the cell that contain many genes). For all genes, there are two copies. One copy is inherited from the mother and the other copy from the father. Recessive means that two copies of the IDUA gene with changes or mutations have to be inherited in order to cause MPS I.

The life expectancy of people with mucopolysaccharidosis type I (MPS I) depends on what type of MPS I they have and the effectiveness of the treatment. The number and severity of symptoms can vary a lot between people who have MPS I. Some people with MPS I have little to no enzyme (α-L-iduronidase), which means their symptoms appear in early childhood. Children with the severe form of MPS I (Hurler syndrome) usually develop normally for the first few years of life, but symptoms can first start appearing between six months of age and two years. Without treatment, by the age of 3 or 4, they begin to lose their cognitive and developmental skills until they can no longer walk or talk. They become severely intellectually disabled. These children have most of the symptoms associated with MPS I and the symptoms are often severe. Without any treatment, children with severe MPS I usually do not survive beyond the age of 10 years.

Some people who have MPS I do not have intellectual disability. These people have attenuated MPS. As MPS I disease progresses, complications become debilitating and often life threatening. It is difficult to predict survival for people who have attenuated MPS I as every patient has different symptoms and severity. Some people do not survive past adolescence or early adulthood, while others survive into their 50s and can have a normal life expectancy. The eventual cause of death is often related to problems with the heart and/or lungs.

Treatment, but no cure, is available for people with mucopolysaccharidosis I (MPS I). There is an FDA-approved enzyme replacement therapy (ERT) called Aldurazyme (laronidase). Aldurazyme is also approved in the EU and other countries around the globe Aldurazyme is given every week by an intravenous (IV, or needle placed into a vein) infusion over about 4 hours for the rest of a person's life. It can improve lung function, increase the range of motion in joints, increase endurance, and reduce the enlarged organs to a normal size. Aldurazyme is not able to reach the brain when given by IV infusion. Therefore, it does not treat the cognitive and developmental regression seen in children with the severe form of MPS I. It is recommended that children with the severe form of MPS I receive a hematopoietic stem cell transplant (HSCT, also called a bone marrow transplant) before 2 years of age. In this procedure, children are given cells that make the alpha-L-iduronidase enzyme from a donor who does not have MPS I. The cells engraft, or seed, into the bone marrow and begin producing the alpha-L-iduronidase enzyme. The cells continue producing the enzyme for the rest of a person's life. The cells are distributed all over the body, including the brain. HSCT is able to prevent or stabilize cognitive and developmental regression (intellectual disability and loss of skills) in children with severe MPS I. It is not able to improve regression (give back skills that have been lost). This is why it should be done before 2 years of age, so children may receive it before they start regressing. HSCT also helps the other symptoms of MPS I, except for many of the bone problems and the corneal clouding. There are many risks associated with HSCT, and some are life threatening. HSCT is considered "worth the risk" in children with the severe form of MPS I, but not in people with attenuated MPS I. The corneal clouding in people with MPS I can be treated with corneal transplants. The cloudy corneas are removed from the eye and replaced with clear corneas from a donor who did not have MPS I. The clear corneas graft, or heal, onto the eyes of the person with MPS I. The corneas remain clear for the rest of the person's life.

To have your child evaluated for MPS I, a good place to begin would be a center that specializes in MPS diseases. The National MPS Society has compiled a list of MPS genetics centers; this can be found by visiting their website at http://mpssociety.org/support/links/. The Oregon Health and Science University has created a map of all the metabolic clinics in the United States to help families find the one closest to them. To search this map, please visit the OHSU website.

SOURCE: Emory University - Department of Human Genetics in collaboration with ThinkGenetic • https://www.thinkgenetic.com/diseases/mucopolysaccharidosis-type-1-3158/overview/6441 • DATE UPDATED: 2017-07-04

References

Clarke LA. Mucopolysaccharidosis Type I. Gene Reviews. www.ncbi.nlm.nih.gov/books/NBK1162/

Hurler Syndrome. NORD Rare disease information. http://rarediseases.org/rare-diseases/mucopolysaccharidosis-type-i/

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