Definition:
Mucopolysaccharidosis I (Hurler/ MPS I) disorders are classified according to the type, severity, and progression of the symptoms. These disorders represent a spectrum of conditions that involve three classifications. The most severely affected individuals are known to have Hurler and the less severely affected individuals are known to have Scheie. There is a wide range of varying severities in between these two benchmark disorders.

Hurler/MPS I is caused by a mutated gene that manufactures the enzyme, alpha-L-iduronidase. The enzyme, which is needed to break down sugars known as glycosaminoglycans or GAGs, is either produced in very low amounts or is completely absent in individuals affected with these disorders. The sugars are used to build tissues, cartilage, skin, tendons, and joint fluid in the body. Individuals affected with Hurler/MPS I have too much GAG in their system. An excessive amount of GAGs lead to the clinical symptoms of Hurler/MPS I.

This disorder affects one in 100,000 individuals worldwide and approximately one in 25,000 children born in the United States will be afflicted with one of the forms of MPS.

Symptoms:
The symptoms of Hurler/MPS I are varied and typically present between one and two years of age. Physical growth typically stops at around three years of age. Some of the hallmark symptoms of these disorders include stiff joints, skeletal abnormalities, clouding of the cornea, an enlarged liver and/or spleen, coarse facial features, thick lips, and an enlarged tongue. Symptoms can also include carpal tunnel syndrome, hearing loss, heart disease, upper respiratory infections, delayed mental development, hernias, fluid on the brain, and lung disease.

Inheritance Pattern:
Hurler/MPS I is an autosomal recessive disorder.

Diagnosis and Testing:
A urine test measuring increased levels glycosaminoglycans (GAGs), the type of sugar chain in the lysosome that accumulate as a result of the malfunctioning enzyme, can determine whether an individual has Hurler/MPSI. A urine test is routinely followed by a blood test or skin biopsy, which will reveal reduced activity of the enzyme alpha-L-iduronidase. Prenatal screening is available to examine alpha-L-iduronidase activity in the fetus. Genetic testing is also available in combination with these diagnostic tests to look for the mutation that causes Hurler/MPS I.

Life Expectancy:
Life expectancy for Hurler/MPS I is 10 years of age or younger.

Treatment:
Treatment for Hurler/MPS 1 includes treating the cause of the disorder as well as some of the symptoms associated. There are various treatments aimed at reducing or controlling the symptoms of this disorder. For instance, supplemental oxygen or a tracheostomy may reduce breathing complications. Physical therapy can alleviate the muscle and joint stiffness associated with this disorder, but will not halt its progression. Surgery may be necessary for a hernia, spinal cord compression, carpel tunnel syndrome, and/or a heart valve replacement.

Enzyme replacement therapy has been utilized to help reduce symptoms of the disorders by supplementing or replacing the absent or deficient enzyme. Since the synthesized enzyme does not cross the blood-brain barrier, this therapy will not affect the neurological symptoms associated with Hurler/MPS I. Bone marrow or stem cell transplantation may also be an option for individuals with severe Hurler/MPS I.

Patient Groups:
National MPS Society
4220 NC Highway 55, Suite 140
Durham NC, 27713
www.mpssociety.org
tel: (919) 806-0101
fax: (919) 806-2005
Barbara Wedehase, Executive Director
info@mpssociety.org