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Diseases

Genetic and Rare Diseases Information Center (GARD)

Mucopolysaccharidosis type I


Other Names for this Disease
  • MPS 1
  • Attenuated MPS I (subtype, includes Hurler-Scheie and Scheie syndrome)
  • Severe MPS I (subtype, also known as Hurler syndrome)
  • Hurler syndrome (subtype)
  • Hurler-Scheie syndrome (subtype)
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.

Your Question

I would like general information on mucopolysaccharidosis I (MPS I). My grandson was recently diagnosed with this condition and is currently undergoing enzyme therapy. Is a person with MPS I less likely to have brain damage if a bone marrow transplant is performed early? 

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

What is mucopolysaccharidosis I?

Mucopolysaccharidosis I (MPS I) is a condition that affects many parts of the body. It is a progressively debilitating disorder; however, the rate of progression varies among affected individuals. MPS I is caused by mutations in the IDUA gene. These mutations lead to reduced levels or the complete lack of the IDUA enzyme. Without the proper amount of this enzyme, large sugar molecules called glycosaminoglycans (GAGs) accumulate within cells called lysosomes. This causes the lysosomes to increase in size, causing many different organs and tissues of the body to become enlarged. This leads to the medical problems seen in the condition.[1][2] 

MPS I was once divided into three separate syndromes: Hurler syndrome, Hurler-Scheie syndrome, and Scheie syndrome, listed from most to least severe. Because no biochemical differences have been identified and the clinical findings overlap, the condition is now divided into two subtypes, severe MPS I and attenuated MPS I.[1][2] People with severe MPS I typically have an earlier onset of symptoms, a decline in intellectual function, and a shorter lifespan. Although there is no cure for MPS I, bone marrow transplant and enzyme replacement therapy are treatment options that may help manage the symptoms of this condition.[1]
Last updated: 2/3/2016

What are the symptoms of mucopolysaccharidosis I?

The signs and symptoms of mucopolysaccharidosis I (MPS I) are not present at birth, but they begin to appear during childhood. People with severe MPS I develop the features of this condition earlier than those with attenuated MPS I. The following list includes the most common signs and symptoms of MPS I:[1]
  • Enlarged head, lips, cheeks, tongue, and nose
  • Enlarged vocal cords, resulting in a deep voice
  • Frequent upper respiratory infections
  • Sleep apnea
  • Hydrocephalus
  • Hepatosplenomegaly (enlarged liver and spleen)
  • Umbilical hernia
  • Inguinal hernia
  • Hearing loss
  • Recurrent ear infections 
  • Corneal clouding
  • Carpal tunnel syndrome
  • Narrowing of the spinal canal (spinal stenosis)
  • Heart valve abnormalities, which can lead to heart failure
  • Short stature
  • Joint deformities (contractures)
  • Dysostosis multiplex (generalized thickening of most long bones, particularly the ribs)
  • Developmental delays and regression 
Last updated: 5/23/2016

What causes mucopolysaccharidosis I?

Mutations in the IDUA gene cause mucopolysaccharidosis I (MPS I). The IDUA gene provides instructions for producing an enzyme (alpha-L-iduronidase) that is involved in the breakdown of large sugar molecules called glycosaminoglycans (GAGs). Mutations in the IDUA gene reduce or completely eliminate the function of alpha-L-iduronidase. This leads to the accumulation of GAGs within cells, specifically inside the lysosomes. Lysosomes are compartments in the cell that digest and recycle different types of molecules. Conditions that cause molecules to build up inside the lysosomes, including MPS I, are called lysosomal storage disorders. The accumulation of GAGs increases the size of the lysosomes, which is why many tissues and organs are enlarged in this disorder.[1][3]
Last updated: 5/23/2016

How is mucopolysaccharidosis I inherited?

Mucopolysaccharidosis I (MPS I) is inherited in an autosomal recessive manner.[1] This means that to be affected, a person must have a mutation in both copies of the responsible gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:
  • 25% (1 in 4) chance to be affected
  • 50% (1 in 2) chance to be an unaffected carrier like each parent
  • 25% chance to be unaffected and not be a carrier
If you are concerned about your risks to be a carrier of MPS I, we would recommend you consult with a genetics specialist, such as a geneticist or a genetic counselor. See our page on how to find a genetics clinic to identify a local genetics specialist.  
Last updated: 5/23/2016

How might mucopolysaccharidosis I be treated?

Management of mucopolysaccharidosis I (MPS I) requires a multidisciplinary team given the wide range of symptoms. This team may include: primary care; cardiology; pulmonology; gastroenterology; neurology; ear, nose, and throat specialists; audiology; ophthalmology; orthopedics; physical therapy; dental; and developmental specialists.[4]

The two main treatment options for MPS I include hematopoietic stem cell transplant (HSCT) and enzyme replacement therapy (ERT). Both of these treatments work by replacing the missing IDUA enzyme (alpha-L-iduronidase).[1]

HSCT is considered standard of care for individuals with severe MPS I; however, its success is dependent on timing of treatment. It is typically recommended that HSCT occur early in the disease process, prior to two years of age. Studies have shown that when successful, HSCT can improve facial, auditory, and cardiac manifestations. The effect on intellectual development is unclear with some studies suggesting an improvement, while others report a slowing of cognitive decline.[4][1]
 
A drug called laronidase or Aldurazyme is the enzyme replacement therapy for MPS I. Treatment with laronidase can improve problems with breathing, growth, the bones, joints and heart. However, this treatment is not expected to treat problems with mental development because laronidase cannot cross the blood-brain barrier.[4][1]

Last updated: 5/23/2016

Is hematopoietic stem cell transplantation effective in reducing the likelihood of brain damage in individuals with mucopolysaccharidosis type I? 

While the effect of hematopoietic stem cell transplantation (HSCT) on intellectual development in individuals with mucopolysaccharidosis type I (MPS I) remains unclear, studies suggest that there is a lower likelihood of problems with intellectual development if HSCT is performed prior to the onset of neurological symptoms. HSCT has been found to stop the damage caused by MPS I before it becomes severe. HSCT may not be helpful for all individuals with MPS I. This surgery has serious risks that must be considered before making treatment decisions.[5]
Last updated: 5/23/2016

References
Other Names for this Disease
  • MPS 1
  • Attenuated MPS I (subtype, includes Hurler-Scheie and Scheie syndrome)
  • Severe MPS I (subtype, also known as Hurler syndrome)
  • Hurler syndrome (subtype)
  • Hurler-Scheie syndrome (subtype)
See Disclaimer regarding information on this site. Some links on this page may take you to organizations outside of the National Institutes of Health.