Mucopolysaccharidosis type I

Alternative names
Alpha-L-iduronate deficiency; Hurler syndrome; MPS I

Definition
Hurler syndrome is an inherited disease that belongs to a group of diseases called mucopolysaccharidoses. Storage of abnormal quantities of this material (mucopolysaccharide) in different body tissues is responsible for the symptoms and appearance of the disease.

Causes, incidence, and risk factors

Hurler syndrome is inherited as an autosomal recessive trait. The metabolic defect that causes Hurler syndrome is the body’s inability to make an enzyme called lysosomal alpha-L-iduronate.

Approximately 1 in 150,000 infants are affected. Newborn infants with this defect appear normal at birth but, by the end of the first year, signs of impending problems begin to develop. The children slowly develop coarse, thick, facial features, prominent dark eyebrows, cloudy corneas, progressive stiffness, and obvious mental retardation.

The disease damages many organs including the heart and heart valves. In the early onset form of the disease, death occurs in the early teens, often from the associated heart disease.

Symptoms

     
  • Short stature  
  • Severe mental retardation  
  • Thick, coarse facial features with low nasal bridge  
  • Full lips with a thick, large tongue  
  • Cloudy corneas  
  • Increased body hair (hirsutism)  
  • Umbilical hernia  
  • Deafness  
  • Stiffness (in joints)  
  • Shortness of breath  
  • Abnormal bones of spine and claw hand

Signs and tests

     
  • Hepatomegaly  
  • Splenomegaly  
  • Inguinal hernia  
  • Flared nostrils  
  • Epicanthal folds  
  • Enlarged tongue  
  • Retinal pigmentation  
  • Hip dislocation  
  • Vertebral wedging  
  • Kyphosis  
  • Heart murmurs  
  • Heart valve damage from thickening

Tests that may indicate the syndrome is present include:

     
  • Increased excretion of dermatan sulfate and heparan sulfate in the urine  
  • Absence of lysosomal alpha-L-iduronidase (in cultured fibroblasts)  
  • Culture of cells from amniotic fluid obtained by amniocentesis for enzyme testing (prenatal testing)  
  • Abnormal histologic staining of white blood cells called metachromasia  
  • X-ray of the skeleton  
  • X-ray of the spine  
  • X-ray of the chest  
  • ECG

Treatment

Enzyme replacement therapy is now possible for patients with a defect in the enzyme a-L-iduronidase. (This includes individuals with Hurler syndrome, but also Scheie and Hurler-Scheie syndromes.) One study examined the effects of this intravenous enzyme replacement in a group of individuals with Hurler syndrome and Scheie syndrome. Many positive benefits were seen, including improved joint mobility, growth (in children), and heart function. Few side effects were reported and the patients tolerated the medication well. How the enzyme replacement affects long-term neurologic function or life-span is still unknown.

Bone marrow transplantation can improve some of the symptoms of the disease. To prevent mental retardation, a bone marrow transplant probably needs to be performed at a very young age. Other treatments depend on the affected organ system.

Support Groups
The National MPS Society
45 Packard Drive
Bangor, ME 04401
207-947-1445
http://www.mpssociety.org

Expectations (prognosis)
Hurler syndrome is a disease with a poor prognosis. Children with this disease have significant progressive physical and mental deficiencies. Death can occur in late childhood, early adolescence, or adulthood.

Complications

     
  • Heart valve damage from thickening or coronary artery disease  
  • Severe mental retardation  
  • Umbilical hernia and inguinal hernia  
  • Deafness  
  • Premature death  
  • Constipation alternating with diarrhea

Calling your health care provider
Call your health care provider if you have a family history of Hurler syndrome and are considering having children, or if your child begins to develop a group of the characteristic signs and symptoms of Hurler syndrome.

Prevention
Genetic counseling is important for prospective parents with a family history of Hurler syndrome. In addition, tests are available for the prenatal diagnosis of Hurler syndrome. The test consists of an amniocentesis and collection of amniotic fluid. Cells in the amniotic fluid are then cultured and the a-L-iduronidase activity in the cells is determined.

Johns Hopkins patient information

Last revised: December 3, 2012
by Gevorg A. Poghosian, Ph.D.

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