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| DiseaseID |
HGD43 |
| Genetic
Disorder |
Hurler Syndrome(MPS)
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| Gene
Name |
IDUA gene |
| Description |
Every substance in the body is important, and has to be present in the right amount. There is a group of genetic disorders called mucopolysaccharidoses (MPS) in which critical body enzymes (chemicals) are missing or not enough. In MPS I, alpha-L-iduronidase is deficient. This enzyme breaks down long chains of sugar molecules so the body can dispose of them. Without the enzyme, the big molecules build up and progressively damage parts of the body.
MPS I is considered to exist on a spectrum from severe to mild (attenuated).
Severe form, also known as Hurler syndrome or MPS I H - Children affected with the severe form may have mental retardation, short stature, stiff joints, speech and hearing impairment, heart disease, pain and a shortened life span.
Mild form, also known as Scheie syndrome or MPS I S - Children born with this form have normal intelligence and may live to adulthood.
Some children may have normal intelligence and mild to severe physical symptoms; this condition may be called Hurler-Scheie syndrome or MPS I H-S.
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| Symptoms |
Symptoms of Hurler syndrome most often appear between ages 3 and 8. Infants with severe Hurler syndrome appear normal at birth. Facial symptoms may become more noticeable during the first 2 years of life.
Symptoms include:
Thick, coarse facial features with low nasal bridge
Halted growth
Progressive mental retardation
Cloudy corneas
Deafness
Joint disease, including stiffness
Heart value problems
Abnormal bones in the spine
Claw hand
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| Causes |
Persons with Hurler syndrome do not make a substance called lysosomal alpha-L-iduronidase. This substance, called an enzyme, helps break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides). These molecules are found throughout the body, often in mucus and in fluid around the joints.
Without the enzyme, glycosaminoglycans build up and damage organs, including the heart. Symptoms can range from mild to severe.
Hurler syndrome is inherited, which means that your parents must pass the disease on to you. Both parents need to pass down the faulty gene in order for you to develop Hurler syndrome.
Hurler syndrome is a type of mucopolysaccharidosis called MPS I. Hurler syndrome is the most severe type. It is categorized as MPS I H.
The other subtypes of MPS I are:
MPS I H-S (Hurler-Scheie syndrome)
MPS I S (Scheie syndrome) |
| Diagnosis |
Diagnosis often can be made through clinical examination and urine tests (excess mucopolysaccharides are excreted in the urine). Enzyme assays (testing a variety of cells or body fluids in culture for enzyme deficiency) are also used to provide definitive diagnosis of one of the mucopolysaccharidoses. Prenatal diagnosis using amniocentesis and chorionic villus sampling can verify if a fetus either carries a copy of the defective gene or is affected with the disorder. Genetic counseling can help parents who have a family history of the mucopolysaccharidoses determine if they are carrying the mutated gene that causes the disorders.
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| Treatment |
Currently there is no cure for these disorders. Medical care is directed at treating systemic conditions and improving the person's quality of life. Physical therapy and daily exercise may delay joint problems and improve the ability to move.
Changes to the diet will not prevent disease progression, but limiting milk, sugar, and dairy products has helped some individuals experiencing excessive mucus.
In 2006, the FDA approved the drug idursulfase (Elaprase) for the treatment of MPS II (Hunter syndrome), the first treatment ever shown to have beneficial effects for people with this condition. A double-blind, placebo-controlled clinical trial in approximately 100 patients with MPS II showed that the drug improved the patients’ ability to walk. Because idursulfase has a number of potentially serious side effects, patients should be monitored carefully when receiving this drug.
Surgery to remove tonsils and adenoids may improve breathing among affected individuals with obstructive airway disorders and sleep apnea. Sleep studies can assess airway status and the possible need for nighttime oxygen. Some patients may require surgical insertion of an endotrachial tube to aid breathing. Surgery can also correct hernias, help drain excessive cerebrospinal fluid from the brain, and free nerves and nerve roots compressed by skeletal and other abnormalities. Corneal transplants may improve vision among patients with significant corneal clouding.
Enzyme replacement therapies are currently in use or are being tested. Enzyme replacement therapy has proven useful in reducing non-neurological symptoms and pain.
Bone marrow transplantation (BMT) and umbilical cord blood transplantation (UCBT) have had limited success in treating the mucopolysaccharidoses. Abnormal physical characteristics, except for those affecting the skeleton and eyes, may be improved, but neurologic outcomes have varied. BMT and UCBT are high-risk procedures and are usually performed only after family members receive extensive evaluation and counseling. |
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