Disorder name: Mucopolysaccharidosis Type I
Acronym: MPS I
- What is MPS I?
- What causes MPS I?
- What are the symptoms of MPS I?
- What is the treatment for MPS I?
- What happens when MPS I is treated?
- What causes the IDUA enzyme to be absent or not working correctly?
- How is MPS I inherited?
- Is genetic testing available?
- What other testing is available?
- Can you test for MPS I during a future pregnancy?
- Can other members of the family have MPS I or be carriers?
- Can other family members be tested?
- How many people have MPS I?
- Does MPS I happen more often in a certain ethnic group?
- Does MPS I go by any other names?
- Where can I find more information?
This fact sheet contains general information about MPS I. Every child is different and some of this information may not apply to your child specifically. Certain treatments may be recommended for some children but not others. If you have specific questions about MPS I and available treatments, you should contact your doctor.
WHAT IS MPS I?
MPS I is an Acquiring a trait from one’s parents. Most traits, such as eye color or hair color, are inherited from a parent through genes. disorder that can affect many parts of the body. People with MPS I have problems breaking down substances in the body called glycosaminoglycans (GAGs). MPS I belongs to a group of disorders known as These are a group of rare inherited disorders. People with lysosomal storage disorders have problems with breaking down large molecules within the lysosome. When the enzymes inside lysosomes are missing or not working properly, there can be a buildup of these molecules which causes a variety of health problems.. There are two main types of MPS I: severe MPS I and attenuated MPS I.
|Lysosomal Storage Disorders:
Lysosomal storage disorders (LSDs) are a group of inherited disorders. They are caused by A molecule that helps chemical reactions take place. For example, enzymes in the stomach speed up the process of breaking down food. Each enzyme can participate in many chemical reactions without changing or being used up. that do not work properly. Lysosomes are like recycling centers for cells. They are small sacs filled with many enzymes that help break down large molecules into smaller molecules that the body can re-use. are like recycling centers for The smallest living unit. Cells make up all organs and tissues in multi-cellular organisms, like humans. They can also live independently, as in bacteria and other microorganisms. At a minimum, a cell is surrounded by a membrane, contains DNA at some stage in its life, and is able to replicate itself into two equal parts.. They are small sacs filled with enzymes. These enzymes help break down large molecules into smaller molecules that the body can re-use. People with LSDs are missing enzymes or have non-working enzymes. As a result, these people have problems breaking down certain large molecules into usable forms. This leads to a buildup of these molecules, which causes a variety of problems. The symptoms and treatment vary between LSDs. They can also vary from person to person with the same LSD.
WHAT CAUSES MPS I?
MPS I occurs when an enzyme called alpha-L-iduronidase (IDUA) is missing or not working properly. Normally, IDUA helps cells break down GAGs into smaller particles that can enter the bloodstream and eventually be discarded or reused. When IDUA doesn’t function properly, GAGs accumulate in cell lysosomes, leading to enlarged lysosomes and cell damage.
Individuals with the severe type of MPS I typically have no IDUA enzyme function. Individuals with the attenuated type of MPS I may have some IDUA enzyme function, which leads to less severe symptoms.
WHAT ARE THE SYMPTOMS OF MPS I?
The symptoms of MPS I are mainly a result of cells becoming enlarged due to the build-up of GAGs and the enlargement of the lysosomes.
People with the severe type of the disease tend to show symptoms before one year of age, and are almost always diagnosed by 18 months old. They develop heart and breathing problems that become severe and usually lead to death before ten years of age.
The attenuated type of the disease is more variable. People with attenuated MPS I usually begin to show symptoms between the ages of three and ten. The severity of symptoms varies significantly between individuals. Symptoms are typically less severe than those seen in individuals with the severe type of the disease. Individuals with attenuated MPS I may or may not have a shortened lifespan.
Symptoms can include:
- Developmental delays and loss of skills (regression)
- Larger than normal liver and This is an organ located behind the stomach. It gets rid of old blood cells and helps fight infection. The spleen can enlarge in people with cirrhosis or with certain metabolic disorders. (hepatosplenomegaly)
- Distinctive looking facial features with thickened lips, cheeks, tongue, and nose
- Generalized thickening of most long bones, particularly the ribs (dysostosis multiplex)
- Joint deformities that affect movement (contractures)
- Narrowing of the spinal canal (spinal stenosis)
- Heart valve abnormalities, which can lead to heart failure
- Frequent upper Respiratory infections are any infection that occurs to the respiratory system. The respiratory system is the breathing system. and ear infections
- Enlarged vocal cords, resulting in a deep voice
- A sleep disorder where breathing repeatedly stops and starts throughout a period of sleep, either because the upper airway becomes blocked repeatedly during sleep, or the brain does not send signals needed for breathing.
- Excessive fluid buildup in the brain (This is also sometimes called 'water on the brain.' It occurs when extra fluid builds up in the ventricles - the inner chambers of the brain. It is often caused by a block in one of the chambers of the brain that does not allow the fluid to drain. When fluid builds up, it causes the ventricles and the skull to expand. It can be present at birth or can happen later in life. If it is not treated, it can cause learning disabilities or intellectual disabilities.)
- Hearing loss
- The cornea is the eye, and can become ‘cloudy’ for a variety of reasons.
- Pain, numbness and tingling in the hand and the arm, which is caused by a compressed nerve in the wrist.
- Short stature
- This is an out-pouching of skin over the navel. Babies with untreated congenital hypothyroidism often have umbilical hernias. It can also be the result of a birth defect or may occur as a result of one of a number of other medical conditions.
- When tissue, such as part of the intestine, protrudes through a weak spot of the inguinal canal (groin area).
WHAT IS THE TREATMENT FOR MPS I?
Because MPS I can affect many parts of the body, comprehensive treatment requires a team of many different specialists. All people with MPS I should be seen by a biochemical genetics doctor (or This is a doctor or medical geneticist who has special training in diagnosing and treating metabolic disorders. They often work in university hospitals or large medical centers.). The team may also include neurology (brain doctor), hematology (blood doctor), orthopedics (bone doctor), primary care, cardiology (heart doctor), pulmonology (lung doctor), gastroenterology (liver doctor), audiology (hearing), ophthalmology (eye doctor), rehabilitation specialists (e.g., physical therapist), dental, and developmental specialists.
Children with MPS I are monitored closely for new or worsening issues. They are typically checked yearly for problems of the nerves, heart, bones, airway, sleep, eyes, and hearing. They are also assessed for learning and intellectual differences.
There are two main methods for treating both attenuated and severe MPS I. Both methods aim to replace missing IDUA enzyme activity: When a person does not have enough working red blood cells, they may have a bone marrow transplant. In this surgical procedure, bone marrow is removed from another person (donor) and implanted into the patient. The patient and bone marrow donor must be a genetic match. There are many risks associated with bone marrow transplants. – also called hematopoietic stem cell transplant In this procedure, stem cells from bone marrow, blood, or umbilical cord blood are taken from another person (donor) and implanted into the patient. The patient and donor must be a genetic match. There are many risks associated with stem cell transplants., and A type of therapy that can be used in some metabolic disorders. In people who have certain enzymes either missing or not working correctly, an IV infusion that contains the enzyme can be given. Enzyme replacement therapy is not a cure, but can help with the health problems and symptoms of the disorder..
- Hematopoietic Stem Cell Transplant (HSCT)
Hematopoietic stem cell transplant is the best way to treat severe MPS I, and if it is successful, improvements are seen in survival, growth, facial features, liver and spleen size, hearing, heart disease, and lung disease. HSCT may help the neurologic-symptom individuals with mild disease. HSCT is not a cure but can significantly help some of the symptoms of severe MPS I. It is best if HSCT is done prior to age 2 years.
- Enzyme Replacement Therapy (ERT)
MPS I is caused by not having enough of an enzyme called alpha-L-iduronidase (IDUA). Enzyme replacement therapy gives people a replacement form of that enzyme. This new enzyme replaces the IDUA in people with MPS I. This is a long-term treatment option, but it is not considered a cure. If enzyme replacement therapy is started prior to the onset of symptoms, it can often prevent or reduce the impact of some MPS I symptoms (except brain and central nervous system symptoms).
Supportive therapies can help treat the symptoms of MPS I:
- Physical therapy can help preserve joint function and increase range of motion.
- Wearing sunglasses can help reduce glare resulting from corneal clouding.
- Hearing aids may be considered in individuals experiencing hearing loss.
- Removal of the tonsils and adenoids can help decrease upper airway obstruction.
WHAT HAPPENS WHEN MPS I IS TREATED?
When HSCT is started early enough in those affected by severe MPS I (ideally before about 16 months – two years of age), cognitive decline may be slowed or even halted. This treatment can also improve other features such as cardiac, facial appearance, liver and spleen enlargement, joint symptoms, and hearing symptoms. However, significant bone, joint, and heart valve disease may still occur despite HSCT.
ERT can improve problems with breathing, growth, joints, and the heart, but cannot treat cognitive symptoms. If started early, it may improve bone problems.
ERT can improve liver size, linear growth, joint mobility, breathing, and sleep apnea in individuals with the attenuated type of MPS I.
WHAT CAUSES THE IDUA ENZYME TO BE ABSENT OR NOT WORKING CORRECTLY?
Genes tell the body how to make enzymes. The IDUA gene instructs the body to make the IDUA enzyme. Everyone has two copies of the IDUA gene. People with MPS I have changes, also called A variant is a change or alteration in a person’s DNA sequence. Variants can happen in genes and affect how the gene functions. There are different types of variants – they can be non-problem causing (benign), disease-causing (pathogenic) or of unknown significance. The term variants is now used in place of the term mutation., in both copies of their IDUA A segment of DNA that contains the instructions to make a specific protein (or part of a protein). Genes are contained on chromosomes. Chromosomes, and the genes on those chromosomes, are passed on from parent to child. Errors in the DNA that make up a gene are called variants and can lead to diseases.. Because of the variants in the IDUA genes, the IDUA enzyme either does not work properly or is not made at all.
HOW IS MPS I INHERITED?
MPS I is inherited in an autosomal recessive manner. It affects both boys and girls equally.
Everyone has a pair of genes that make the IDUA enzyme. In people with MPS I, neither of the IDUA genes work correctly. These individuals inherit one non-working IUDA gene for the condition from each parent.
Parents of children with MPS I usually do not have the condition themselves. Instead, each parent has one non-working IUDA gene and one working IUDA gene. The parents are called A person who has one copy of a gene mutation for a particular autosomal recessive disorder (remember genes come in pairs). Carriers are not affected by the disorder. However, they can pass on the gene variant to their children. Children who inherit two such gene variants will be affected by the disorder. The term variants is now used in place of the term mutation.. Carriers do not have MPS I because one of their genes is working correctly. The working IDUA gene is able to make enough IDUA enzyme for the person to be healthy.
When both parents are carriers, each pregnancy has a 25% (1 in 4) chance of resulting in a child having MPS I (has the disorder). There is a 50% (1 in 2) chance for the child to be a carrier, just like the parents. There is a 25% (1 in 4) chance that the child will have two working genes (normal).
Relating to (or due to) genes and heredity or the field of studying genes and heredity. counseling is available to families who have children with MPS I. Genetic counselors can answer questions about how MPS I is inherited, choices during future pregnancies, and how to test other family members. Ask your doctor about a referral to a These are health care providers who have special training in genetic conditions. They help families understand genetic disorders and how they are passed down. Genetic counselors offer information and support to people who have genetic conditions in their families or are concerned that they may have a child with an inherited disorder..
IS GENETIC TESTING AVAILABLE?
A diagnosis of MPS I is usually made based on a doctor’s evaluation and genetic testing. Genetic testing and enzyme testing for MPS I can be done on a blood sample. Genetic testing, also called DNA testing, looks for changes (variants) in the IUDA genes that cause MPS I.
Because MPS I may be diagnosed by enzyme testing, Deoxyribonucleic acid (DNA) is a molecule found in the chromosomes that carries genetic information. DNA is composed of four units (called bases) that are designated A, T, G, and C. The sequence of the bases spell out instructions for making all of the proteins needed by an organism. A gene is a section of DNA that holds the instructions for a specific protein. A change in one or more of the DNA bases making up a gene is called a mutation. Some mutations change the protein instructions and can lead to particular health problems or disorders. Each parent passes half of their chromosomes, and thus half of their DNA instructions, onto their children. It is these instructions that cause certain traits, such as eye or hair color, to be inherited. testing is not always necessary to diagnose your child. It is helpful to know the gene changes in a child with MPS I because it can help with testing in other family members and in prenatal testing of a future pregnancy.
WHAT OTHER TESTING IS AVAILABLE?
The process of testing for disease in a person who does not show signs of having the disease (nonsymptomatic or asymptomatic person). The goal of screening is to catch the disease in its early stages. Tests
A screening test that looks for different disorders using a small sample of blood taken from a newborn’s heel. A positive or abnormal newborn screening result means that there are slight differences that were found in the baby’s blood, and further testing is needed to figure out if the baby has a metabolic disorder.
Newborn screening for MPS I is done in some states. A blood spot from the baby’s heel is used to screen for many different conditions. Newborn screening detects MPS I by looking for IDUA enzyme activity. IDUA enzymes are active in every healthy newborn’s blood. Since babies with MPS I have IDUA enzymes that are either missing or not working properly, they will have reduced enzyme activity.
If your child has had a positive screen for MPS I through a newborn screening program, it does not yet mean that he or she has MPS I. Other tests still need to be done in order to confirm the diagnosis.
When one or both parents are known to be carriers of the MPS I disease, newborn screening results are not enough to rule out MPS I disease in a newborn baby. In this case, more sensitive diagnostic testing should be done in addition to newborn screening, even if the newborn screening result is negative.
Confirmatory testing is needed for a diagnosis of MPS I. Each person may not need every one of the confirmatory tests.
Some of these special tests detect the amount of GAGs and IDUA enzymes in your baby’s blood and urine. These blood or urine tests may be helpful to determine whether your child needs treatment, and then later to see whether treatment is working properly.
Genetic testing of the IDUA gene may be necessary after newborn screening.
CAN YOU TEST FOR MPS I DURING A FUTURE PREGNANCY?
Once a genetic cause has been identified, DNA from the fetus can be tested. The sample for this testing is obtained by either chorionic villus sampling CVS or This is a test done during pregnancy. A needle is used to remove a small sample of fluid from the sac around the fetus. The sample can be used to test for certain genetic disorders in the fetus. Amniocentesis to test for genetic conditions is usually done between 13 and 20 weeks of pregnancy..
Parents may choose to have testing during pregnancy or wait until birth to have the baby tested. Parents may also choose to use assisted reproductive techniques to decrease the chance that their future children would have MPS I. A genetic counselor can talk to you about your choices and answer questions about prenatal testing or testing your baby after birth.
CAN OTHER MEMBERS OF THE FAMILY HAVE MPS I OR BE CARRIERS?
Having MPS I
Each full A person who shares the same mother or father. A brother or sister who shares both parents is called a full sibling. A brother or sister who only shares one parent is called a half sibling. (same mother and father) of a baby with MPS I has a 25% (1 in 4) chance of also having MPS I. Even older siblings who have not shown any symptoms of the disease could have attenuated MPS I that has not caused symptoms yet, but will in the future. All siblings of an individual with MPS I should be evaluated to see if they also have this disorder.
Not all states offer newborn screening for MPS I. Even if your baby’s siblings have had normal newborn screening, they should be tested specifically for MPS I because early treatment can prevent more serious health problems. Talk to your doctor or genetic counselor about testing your other children for MPS I.
Carrier for MPS I
Each full sibling of a baby with MPS I has a 50% (1 in 2) chance of being a carrier. Full siblings who do not have MPS I have a 66% (2 in 3) chance of being a carrier. If you are a parent of a child with MPS I, your brothers and sisters have a 50% (1 in 2) chance of being a carrier. It is important for other family members to be told that they could be carriers. There is a small chance that they are also at risk to have children with MPS I.
Not all states offer newborn screening for MPS I. This makes it especially important to tell your family members if they are at risk for having a child with the disease.
CAN OTHER FAMILY MEMBERS BE TESTED?
Siblings of a child with MPS I should be tested. Talk to your doctor or genetic counselor if you have questions about testing for MPS I.
If both gene variants have been found in your child, other family members can have DNA testing to see if they are carriers. If you have questions about carrier testing, ask your genetic counselor or doctor.
HOW MANY PEOPLE HAVE MPS I?
MPS I is seen in all populations and about 1 in 100,000 people have the severe type and 1 in 500,000 have the attenuated type.
DOES MPS I HAPPEN MORE OFTEN IN A CERTAIN ETHNIC GROUP?
MPS I occurs in people of all ethnic groups around the world.
DOES MPS I GO BY ANY OTHER NAMES?
MPS I is also known as:
- Hurler A group of symptoms and clinical findings that, when found together, make up a particular condition or disease.
- Hurler-Scheie syndrome
- Scheie syndrome
- Alpha-L-Iduronidase deficiency
- IDUA deficiency
- Attenuated MPS I
- Severe MPS I
WHERE CAN I FIND MORE INFORMATION?
National MPS Society
Canadian Society for Mucopolysaccharide and Related Diseases Inc. (Canadian MPS Society):
|Reviewed by:||HI, CA, OR, and WA metabolic specialists|
|Review date:||March 30, 2018
June 1, 2020
March 16, 2023
|Update on:||March 16, 2023|
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