Mucopolysaccharidosis Type I (MPS I)
What causes someone to have MPS I?
MPS I is caused by the deficiency of the enzyme alpha-L-iduronidase. This enzyme is responsible for breaking down certain compounds called GAGs (glycosaminoglycans) in a compartment of the cell called a lysosome. In MPS I, the deficiency of alpha-L-iduronidase causes GAG to build up in the lysosome. With time, more and more GAG builds up in the lysosomes in various body tissues. The progressive accumulation of glycogen causes the symptoms we see in individuals with MPS I.
MPS I includes Hurler syndrome, Hurler-Scheie syndrome and Scheie syndrome.
Are there different types of MPS I? How do the types differ?
MPS I is commonly divided into three "types" of MPS I. These are Hurler syndrome, Hurler-Scheie-syndrome and Scheie syndrome. All three types have the same underlying cause. The three types differ based on the body systems affected, the degree of invovlement and the severity of the disease.
Individuals with Hurler syndrome (MPS IH) show their first symptoms during their first year of life, although the condition is sometimes not recognized until they are older. Children with MPS IH have symptoms that progress more quickly than individuals with the other types of MPS I. They also have developmental delays that become more severe as they age.
Individuals with Scheie syndrome (MPS IS) have a type of MPS I that does not affect the ability to learn. The symptoms of MPS IS progress more slowly than the other types of MPS I. Although the term "mild" is often used to describe MPS IS, this can be deceiving, as MPS IS can cause significant health problems and physical challenges for affected individuals.
Hurler-Scheie syndrome (MPS IHS) is used to describe the intermediate form of MPS I. Individuals with MPS IHS have symptoms in early childhood that progress over time. Intelligence may or may not be affected in individuals with this type of MPS I.
How common is MPS I?
Studies show that about 1 in every 100,000 newborns has MPS I. Of the three types, MPS IH is the most common.
What are the signs and symptoms of MPS I?
Height
During the first year of life, individuals with MPS IH are usually bigger than other babies. After the first year or two, individuals with all types of MPS I are usually shorter than their peers.
Brain and central nervous system
Children with MPS IH begin to show delays in development at 12 to 24 months of age. The developmental delay is progressive and can cause children to lose previously learned skills. Intelligence is typically not affected by the other forms of MPS I (Hurler-Scheie and Scheie syndromes).
Children with MPS IH can also develop hydrocephalus (increased pressure in the brain due to an increase in cerebrospinal fluid).
Appearance
Individuals with MPS I tend to have shorter noses, thicker eye brows and coarser hair than their family members. Changes in bone shape and joint problems can also affect how a person looks.
Ear, Nose, and Throat
MPS I often causes frequent ear infections, which can affect hearing and cause pain. Runny noses are common, even when a person does not have a cold. The tonsils and adenoids may be enlarged, which can cause snoring and sleep apnea (interruptions in breathing during sleep).
Breathing
Breathing can be affected by MPS I. Nighttime breathing problems, such as snoring and sleep apnea, can occur due to enlarged tonsils and adenoids. Daytime breathing problems can be caused by a short chest cavity, small airway passages and compression of the lungs by an enlarged liver and spleen. As the disease progresses, the breathing problems can be serious and may become life threatening.
Eyes
Clouding of the cornea may be present during the first year of life. Individuals with MPS I may also experience retinal and optic nerve changes that can cause vision loss and glaucoma. Blindness is common in later stages of disease.
Heart
As the GAG material builds up in the heart, the heart can show progressive symptoms. Problems with the heart valves and an enlarged heart are the most common heart problems experienced by individuals with MPS I.
Abdomen
The liver and spleen are often enlarged, due to storage of the GAG material in these organs. The enlarged liver and spleen make the abdomen bigger, which can make the person look overweight. The enlargement of the liver and spleen does not affect how these organs work.
Hernias are also common in individuals with MPS I. Hernias, especially those that occur at the belly button, are usually present within the first year of life. Hernias that are surgically repaired may reoccur following surgery.
Bones and joints
Bone and joint problems are common in individuals with all types of MPS I. Joint stiffening and bone changes in the hands can severely limit the flexibility and use of the fingers and hand.
Babies with MPS IH may be born with a "bump" on the lower or middle back, caused by unusually-shaped vertebrae. This bump is called a "gibbus" and does not occur if it is not present at birth.
People with all types of MPS I often have limited range of motion at some joints. For example, many people with MPS I are unable to raise their arms over their heads. Joint changes can also cause pain and arthritis in the joints. These symptoms can be progressive and can have a significant effect on daily life and activities.
Carpal tunnel syndrome is also common in individuals with MPS I. This can lead to pain and affect use of the hands.
How is MPS I diagnosed?
A doctor may suspect MPS I or a related condition based on the person's symptoms. However, one specific test must be ordered to confirm a diagnosis of MPS I. MPS I occurs when the body does not make enough alpha-L-iduronidase, an enzyme that is responsible for breaking down specific compounds called glycosaminoglycans (GAGs) in the cells of the body. The test measures the amount of alpha-L-iduronidase in blood or skin cells. A person with MPS I will have less than 1 percent of the usual amount of alpha-L-iduronidase in their cells.
Prenatal testing for MPS I is also available during pregnancy. Amniocentesis can be performed, and enzyme activity can be measured in cells grown from the amniocentesis sample.
What kinds of treatment are available for MPS I?
There is no cure for MPS I at this time.
Enzyme replacement therapy (ERT) is a treatment in which a man-made form of the missing enzyme (alpha-L-iduronidase) is given intravenously (by IV) once per week. The man-made enzyme slows or stops the progression of many symptoms of the disease. However, the man-made enzyme is not able to prevent progressive learning problems or prevent bone problems. The Cincinnati STAR Center for Lysosomal Diseases offers treatment with ERT for all types of MPS I.
A bone marrow, stem cell or cord blood transplant may be considered for individuals with MPS IH. A successful transplant can slow or stop the progression of many disease symptoms, including the ability to learn. A successful transplant does not prevent bone problems. Cincinnati Children's Hospital Medical Center offers transplants to children with MPS IH.
Living with the daily challenges and uncertainty of a chronic illness is often difficult and stressful for affected individuals and their families. Individuals with chronic illness and their loved ones are at increased risk to develop depression. Psychologists, family counselors or marriage therapists help families cope with the difficulties of living with a chronic illness.
Geneticists, pediatricians and family care physicians, internists, pulmonologists, respiratory therapists, orthopedic specialists, cardiologists, and physical and occupational therapists are some of the medical professionals that may be a part of the medical team caring for a child or adult with MPS I.
Is research being done on MPS I?
The Cincinnati STAR Center for Lysosomal Diseases is currently participating in a patient registry for MPS I. This registry is being used internationally to collect information on individuals with MPS I. The information collected will be used to help physicians develop a better understanding of the condition and how it affects people. If you are interested in participating in the MPS I Registry, you can contact the Cincinnati STAR Center for Lysosomal Diseases at 1-800-647-4805.
The National Institutes of Health (NIH) maintains a web site that lists many clinical trials recruiting participants in the United States. To search for clinical trials, visit www.clinicaltrials.gov
Where can I go to get more information on MPS I?
Cincinnati STAR Center for Lysosomal Diseases
Telephone: 1-800-647-4805
Fax: 513-636-0124
Mail: Cincinnati STAR Center for Lysosomal Diseases
C / o Debbie Baker
Cincinnati Children's Hospital Medical Center
Division of Human Genetics
3333 Burnet Avenue ML 4006
Cincinnati, OH 45229
National MPS Society
www.mpssociety.org
The National MPS Society supports research, provides support to individuals and their families affected by an MPS disease, and promotes public and professional awareness of these conditions.
National Organization for Rare Disorders (NORD)
http://www.rarediseases.org/
NORD is an organization dedicated to helping people with rare diseases. It works toward diagnosing, treating and curing rare disorders through programs of education, advocacy, research and service.
Written 2/05
