Mucopolysaccharides Mucopolysaccharides are long chains of sugar molecules that are found throughout the body, often in mucus

and in fluid around the joints. They are more commonly called glycosaminoglycans. Information When the body cannot break down mucopolysaccharides, a condition called mucopolysaccharidoses (MPS) occurs. MPS refers to a group of inherited disorders of metabolism. People with MPS do not have any, or enough of, a substance (enzyme) needed to break down the sugar molecule chains. These conditions cause mucopolysaccharides to build up in body tissues. This can damage organs, including the heart. Symptoms can range from mild to severe and may include:

Abnormal features of the face Bone, cartilage, and connective tissue deformities Mental retardation

Hunter syndrome Hunter syndrome is an inherited disease in which long chains of sugar molecules (mucopolysaccharides) are not broken down correctly and build up in the body. Causes Hunter syndrome is an inherited condition. Boys are most often affected. The condition is caused by a lack of the enzyme iduronate sulfatase. Without this enzyme, mucopolysaccharides build up in various body tissues, causing damage. The early-onset, severe form of the disease begins shortly after age 2. A late-onset, mild form causes less severe symptoms to appear later in life. Symptoms Juvenile form (early-onset, severe form): Aggressive behavior Hyperactivity Mental function gets worse over time Severe mental retardation Spasticity Late (mild) form:
Mild to no mental deficiency Both forms:

Carpal tunnel syndrome Coarse features of the face Deafness (gets worse over time) Increased hair (hypertrichosis) Joint stiffness Large head (macrocephaly)

Exams and Tests Signs of the disorder include: 1

Abnormal retina (back of the eye) Decreased iduronate sulfatase enzyme in blood serum or cells Heart murmur and leaky heart valves Enlarged liver (hepatomegaly) Enlarged spleen (splenomegaly) Inguinal hernia Joint contractures Spasticity Tests may include:

Enzyme study Genetic testing for change (mutation) in the iduronate sulfatase gene Urine test for heparan sulfate and dermatan sulfate

Treatment The U.S. Food and Drug Administration has approved the first treatment for Hunter syndrome. The medicine, called idursulfase (Elaprase), is given through a vein (intravenously). Talk to your doctor for more information. Bone marrow transplant has been tried for the early-onset form, but the results can vary. Each health problem should be treated separately. Outlook (Prognosis) People with the early-onset (severe) form usually live for 10 - 20 years. People with the late-onset (mild) form usually live 20 - 60 years. Possible Complications

Airway obstruction Carpal tunnel syndrome Hearing loss that gets worse over time Loss of ability to complete daily living activities Joint stiffness that leads to contractures Mental function that gets worse over time

When to Contact a Medical Professional Call your health care provider if:

You or your child has a group of these symptoms You know you are a genetic carrier and are considering having children

Prevention Genetic counseling is recommended for couples who want to have children and who have a family history of Hunter syndrome. Prenatal testing is available. Carrier testing for female relatives of affected males is available at a few centers. Alternative Names Mucopolysaccharidosis type II, Iduronate sulfatase deficiency Hurler syndrome Hurler syndrome is a rare, inherited disease of metabolism in which a person cannot break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides). 2

Hurler syndrome belongs to a group of diseases called mucopolysaccharidoses, or MPS.

Causes Persons with Hurler syndrome do not make a substance called lysosomal alpha-L-iduronidase. This substance, called an enzyme, helps break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides). These molecules are found throughout the body, often in mucus and in fluid around the joints. Without the enzyme, glycosaminoglycans build up and damage organs, including the heart. Symptoms can range from mild to severe. Hurler syndrome is inherited, which means that your parents must pass the disease on to you. Both parents need to pass down the faulty gene in order for you to develop Hurler syndrome. Hurler syndrome is a type of mucopolysaccharidosis called MPS I. Hurler syndrome is the most severe type. It is categorized as MPS I H. The other subtypes of MPS I are:

MPS I H-S (Hurler-Scheie syndrome) MPS I S (Scheie syndrome)

Symptoms Symptoms of Hurler syndrome most often appear between ages 3 and 8. Infants with severe Hurler syndrome appear normal at birth. Facial symptoms may become more noticeable during the first 2 years of life. Symptoms include:

Abnormal bones in the spine Claw hand Cloudy corneas Deafness Halted growth Heart value problems Joint disease, including stiffness Mental retardation that gets worse over time Thick, coarse facial features with low nasal bridge

Exams and Tests

EKG Genetic testing for the alpha-L-iduronidase (IDUA) gene Urine tests for extra mucopolysaccharides X-ray of the spine

Treatment Enzyme replacement therapy adds a working form of the missing enzyme to the body. Bone marrow transplant has been used in several patients with this condition. The treatment has had mixed results. Other treatments depend on the organs that are affected. Outlook (Prognosis) 3

Hurler syndrome is a disease with a poor outlook. Children with this disease develop nervous system problems, and can die young. Prevention Experts recommend genetic counseling and testing for couples with a family history of Hurler syndrome who are considering having children.

Alternative Names Alpha-L-iduronate deficiency; Mucopolysaccharidosis type I; MPS I H Sanfilippo syndrome Sanfilippo syndrome is metabolism disorder passed down through families. It makes the body unable to properly break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides). The syndrome belongs to a group of diseases called mucopolysaccharidoses (MPS). Specifically, it is known as MPS III. Causes Sanfilippo syndrome occurs when the substances (enzymes) needed to break down the heparan sulfate sugar chain are missing or are defective. There are four main types of Sanfilippo syndrome, also called MPS III. Which type a person has depends on which enzyme is affected. Sanfilippo type A is the most severe form. Persons with this type are missing or have an altered form of an enzyme called heparan N-sulfatase. Sanfilippo type B occurs when a person is missing or doesn't not produce enough alpha-N-acetylglucosaminidase. Sanfilippo C occurs when a person is missing or doesn't not produce enough acetyl-CoAlpha-glucosaminide acetyltransferase. Sanfilippo D occurs when a person is missing or doesn't not produce enough N-acetylglucosamine 6-sulfatase. The syndrome is inherited as an autosomal recessive trait. That means both your parents must pass you the defective gene in order for you to get this disease. Sanfilippo syndrome is possibly the most common forms of MPS. It is seen in about 1 in 70,000 births. A family history of Sanfilippo syndrome increases one's risk for this condition. Symptoms Unlike other forms of MPS, symptoms appear after the first year of life. A decline in learning ability typically occurs between ages 2 and 6. The child may have normal growth during the first few years, but final height is below average. Delayed development is followed by deteriorating mental status. Other symptoms include:

Behavioral problems Coarse facial features Diarrhea Full lips Heavy eyebrows that meet in the middle of the face above the nose Sleep difficulties Stiff joints that may not extend fully Walking problems 4

Exams and Tests A physical exam may show signs of liver and spleen swelling. An eye exam will show clear corneas, unlike the cloudy corneas seen in persons with Hurler syndrome (MPS I H). Neurological testing will reveal signs of seizures and mental retardation. Urine tests will be done. Persons with Sanfilippo syndrome have large amounts of a mucopolysaccharide called heparan sulfate in the urine. Other tests may include:

Blood culture Echocardiogram Slit lamp eye exam Skin fibroblast culture X-rays of the bones

Treatment There is no specific treatment available for Sanfilippo syndrome. Outlook (Prognosis) The syndrome causes significant neurological symptoms, including severe retardation. IQs may be below 50. Most persons with Sanfilippo syndrome live into their teenage years. Some patients live longer, while others with severe forms die at an earlier age. Symptoms appear most severe in persons with type A Sanfilippo syndrome. Possible Complications

Blindness Inability to care for self Mental retardation Nerve damage that slowly gets worse and eventually requires wheelchair use Seizures

Prevention Genetic counseling is recommended for prospective parents with a family history of Sanfilippo syndrome. Counseling is also recommended for families who have a child with Sanfilippo syndrome, to help them understand the condition and possible treatments. Alternative Names MPS III Scheie syndrome Scheie syndrome is metabolism disease passed down through families in which the body cannot properly break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides). The syndrome belongs to a group of diseases called mucopolysaccharidoses (MPS). Specifically, it is known as MPS I S. Causes Persons with Scheie syndrome are missing a substance called lysosomal alpha-L-iduronidase. This substance, called an enzyme, helps break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides). These molecules are found throughout the body, often in mucus and in fluid around the joints. 5

Without the enzyme, glycosaminoglycans build up. This excess material is stored in body tissues and can damage organs, including the heart. Symptoms can range from mild to severe. Scheie syndrome is the mildest form of mucopolysaccharidosis type 1. The syndrome is transmitted as an autosomal recessive trait. That means that both parents must pass along the defective gene for the offspring to have the disease. Symptoms Symptoms may not appear until age 4 or 5, and may include:

Broad mouth with full lips Claw hands and deformed feet Cloudy cornea and progressive loss of vision, resulting in blindness Coarsened facial features Increased body hair (hirsutism) Prognathism Stiff joints

Exams and Tests A physical exam may show signs of: Aortic regurgitation Hearing loss Hernias -- inguinal hernia, umbilical hernia Liver swelling Prognathism An eye exam will show cloudy corneas and retinal pigmentation. Urine tests will be done. Persons with Scheie syndrome have increased amounts of dermatan and heparan sulfate in their urine. See: Urine dermatan sulfate Other tests may include:

Blood culture Culture of skin fibroblasts Echocardiogram X-ray of the skeleton

Treatment Enzyme replacement therapy for patients with a defect in the enzyme a-L-iduronidase is now possible. This includes individuals with Scheie syndrome, but also Hurler and Hurler-Scheie syndromes. Early recognition and treatment of spinal cord compression can prevent permanent nerve damage. Treatment is also given for heart problems caused by leaky valves. Outlook (Prognosis) Scheie syndrome is compatible with an almost normal lifespan. However, some disabilities such as limitation of joints, blindness, or deafness are likely to occur later in life. Possible Complications

Compression of the spinal cord, which can lead to loss of nerve function Extremity deformities Hearing loss and deafness 6

Problems with the aortic valve Vision problems

Prevention Genetic counseling is recommended for prospective parents with a family history of Scheie syndrome. Counseling is also recommended for families who have a child with Scheie syndrome, to help them understand the condition and possible treatments. Alternative Names Mucopolysaccharidosis type I S; MPS I S Morquio syndrome Morquio syndrome is an inherited disease of metabolism in which the body is missing or doesn't have enough of a substance needed to break down long chains of sugar molecules called glycosaminoglycans (formerly called mucopolysaccharides). The syndrome belongs to a group of diseases called mucopolysaccharidoses (MPS). Specifically, it is known as MPS IV.

Causes Morquio syndrome is an autosomal recessive trait. That means both your parents must pass you the defective gene in order for you to get this disease. There are two forms of Morquio syndrome: Type A and Type B. Persons with Type A do not have a substance (enzyme) called galactosamine-6-sulfatase. Persons with Type B do not produce enough of an enzyme called beta-galactosidase. The body needs these enzymes to break down a long strand of sugar molecules called the keratan sulfate sugar chain. In both types, abnormally large amounts of glycosaminoglycans build up in the body and brain, which can damage organs. The syndrome is estimated to occur in 1 of every 200,000 births. Symptoms usually start between ages 1 and 3. A family history of the syndrome raises one's risk for the condition. Symptoms

Abnormal development of bones, including the spine Bell-shaped chest with ribs flared out at the bottom Coarse facial features Hypermobile joints Knock-knees Large head (macrocephaly) Short stature with a particularly short trunk Widely spaced teeth

Exams and Tests The doctor will perform a physical examination. Examination and testing may reveal:

Abnormal curvature of the spine (kyphoscoliosis) Cloudy cornea Heart murmur (aortic regurgitation) 7

Inguinal hernia Liver enlargement Loss of nerve function below the neck Short stature (especially short trunk) Urine tests are usually done first. These tests may show extra mucopolysaccharides, but they can't determine the specific form of MPS. Other tests may include: Blood culture Echocardiogram Genetic testing Hearing test Slit-lamp eye exam Skin fibroblast culture X-rays of the long bones, ribs, and spine Persons with Morquio syndrome should have MRI of the lower skull and upper neck to determine if the upper vertebrae are underdeveloped. Treatment There is no specific treatment for Morquio syndrome. Researchers are currently testing a possible treatment involving enzyme replacement. Symptoms are treated as they occur. A spinal fusion may prevent permanent spinal cord injury in persons whose neck bones are underdeveloped. Outlook (Prognosis) Cognitive (thinking) function is usually normal in patients with Morquio syndrome. Bone problems can lead to significant complications. For example, the small bones at the top of the neck may slip and damage the spinal cord, causing paralysis. Surgery to correct such problems should be done if possible. Heart (cardiac) complications may lead to death. Possible Complications

Breathing problems Heart failure Spinal cord damage and possible paralysis Vision problems Walking problems related to abnormal curvature of the spine and other bone problems

Prevention Genetic counseling is recommended for prospective parents with a family history of Morquio syndrome. Counseling is also recommended for families who have a child with Morquio syndrome, to help them understand the condition and possible treatments. Alternative Names Mucopolysaccharidosis type IVA; Galactosamine-6-sulfatase deficiency; Mucopolysaccharidosis type IVB; Beta galactosidase deficiency; MPS IV