Mucopolysaccharidosis is part of a group of disorders called lysosomal storage diseases. These disorders occur when enzymes in cells that break down complex molecules are missing or don’t work properly.
These enzymes are needed to degrade glycosaminoglycans (GAGs), which make up bone, cartilage, tendons, corneas and other tissues. Without them, GAGs build up in cells, blood and connective tissue over time, causing a wide range of symptoms.
Types
In mucopolysaccharidosis disorders, the enzymes that normally break down glycosaminoglycans do not work properly. This results in a build-up of these building blocks of connective tissue, which interferes with normal development and function. People with the seven different types of mucopolysaccharidosis experience a variety of symptoms, depending on the type of disorder and its severity. The build-up of glycosaminoglycans can lead to damage throughout the body, including the brain and spinal cord, heart valves, eyes, and connective tissues.
Mucopolysaccharidosis is part of the group of lysosomal storage disorders, which occur when the body’s specialized recycling center, called a lysosome, cannot break down waste products. The lysosome contains special enzymes that turn unwanted materials into substances the cell can use. These disorders occur when these enzymes exist in too small an amount or are missing altogether.
Glycosaminoglycans are a major component of many organs and tissues, including the skin, blood, bones, and lungs. They also play an important role in the formation of collagen, which is a protein that helps hold cells together. Glycosaminoglycans break down in the lysosome, but when there is not enough of these enzymes to break them down, they accumulate. The mucopolysaccharidosis are a group of inherited disorders that affect the lysosome’s ability to process these building blocks of connective tissue.
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All the disorders in this group are progressive, meaning that over time, they cause a gradual decline in physical and mental function. Most people with mucopolysaccharidosis have an average life expectancy of about 30 years.
In most cases, symptoms begin during infancy or childhood. Some of the most common signs and symptoms include a delay in growth and development, short stature, coarse hair, and abnormal facial features (see picture).
Some people with severe types of mucopolysaccharidosis may develop a condition called hydrocephalus, which is caused by an increase in fluid pressure in the skull. This can cause headaches, a enlarged head (see picture), and problems with hearing and vision.
The National Institutes of Health, which includes the Eunice Kennedy Shriver National Institute of Child Health and Human Development, is funding research into these disorders to improve treatment options. Lifelong enzyme replacement therapy, sometimes paired with bone marrow or stem cell transplantation, can prevent the disease from getting worse and reverse some of its complications.
Symptoms
The mucopolysaccharidoses are a group of genetic disorders caused by missing or deficient enzymes that break down complex sugar molecules, called glycosaminoglycans. These are the building blocks that form bones, cartilage, tendons and other soft tissues. In the mucopolysaccharidoses, these molecules accumulate in body tissue and cause characteristic facial features and abnormalities of the bones, eye and liver.
These conditions are grouped together because they all involve the same group of enzymes and they are all autosomal recessive disorders. The symptoms vary depending on the specific disorder, with Hurler syndrome being the most severe and Scheie syndrome the mildest.
Most cases of Mucopolysaccharidosis are diagnosed by a physical exam and lab tests, including urine and blood. The vet may also look at your cat’s white blood cells to see if they have large vacuoles and granules present, which is a clear indication of a metabolic disorder like Mucopolysaccharidosis. X-rays and an echocardiogram will be used to diagnose heart problems.
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A person with a mucopolysaccharidosis will have a normal early period of life, but over time their condition will deteriorate, leading to multiple health issues. The signs and symptoms will include poor growth, development delay, frequent ear infections or respiratory infections, bone problems, shortened height, curved spine (scoliosis) and corneal clouding.
Some mucopolysaccharidosis patients have an enlarged liver and spleen, and some develop a type of dementia known as Lewy body disease. Other signs and symptoms include problems with hearing, speech and swallowing, and poor muscle coordination and vision.
Children with the more severe types of mucopolysaccharidosis don’t live very long, especially if they have an untreated form of the disease. However, some children who have the mildest forms of the disease, such as Hurler syndrome, can lead relatively normal lives with treatment that includes enzyme replacement therapy. Support groups for those affected by the condition can help families connect with others who have similar experiences and are able to offer support. These groups can also provide information and educational materials. Some families may also choose to have a bone marrow transplant, which can cure the disease for some patients.
Diagnosis
The mucopolysaccharidosis are a group of rare, multisystemic lysosomal storage diseases caused by the absence or deficiency of enzymes which normally contribute to the degradation of glycosaminoglycans. The accumulation and consequent systemic deposition of partially or undegraded glycosaminoglycans affects all somatic tissues, including the heart. The symptoms of these conditions vary from symptom to symptom and may not become apparent until later in life, when the affected person begins to develop complications from the disorder.
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Children with mucopolysaccharidosis develop short stature and stiff joints, especially in the hands. They may also have a facial appearance marked by a prominent forehead and large head (macrocephaly), and thick hair and eyebrows. They often have a condition called dysostosis multiplex, which refers to skeletal abnormalities that are noted on X-rays and seen as multiple bones sticking out of the skin, or as a bony prominence that sticks out in front of the chest (pectus excavatum). They may also develop hearing loss from hearing difficulties associated with the disease.
In people with MPS I, the deficiency of the enzyme heparan sulfate sulfatase results in a build-up of heparan sulfate and dermatan sulfate in the body. This causes a progressive decline in mental ability, and many affected individuals have a small skull (microcephaly).
A child with MPS II, also known as Hunter syndrome, has a deficiency of the enzyme iduronate-2-sulfatase. This causes a severe disease that can cause heart failure in infancy due to fluid retention and pressure on the heart valves. Children with this disease may have short stature, joint stiffness and restricted movement, and a heart defect with restriction of the mitral valve leaflets.
A doctor can diagnose the various mucopolysaccharidosis disorders by doing a physical exam and taking a family history. They can also check the urine for sugar. These tests, together with a medical history and X-rays of the skeleton and the heart, can help doctors determine which type of mucopolysaccharidosis is present. NINDS, along with the other components of NIH, is conducting long-term research on the mucopolysaccharidosis to learn more about how these genetic disorders affect the brain and body.
Treatment
In some of the mucopolysaccharidosis types, enzymes that break down glycosaminoglycans are missing, and excess GAGs accumulate in cells, tissues, and organs. These inherited metabolic disorders are sometimes fatal in infancy, and some cause progressive decline of physical and mental function over time.
Most types of mucopolysaccharidosis begin in early childhood and are usually diagnosed by examining the affected person and reviewing family history. A blood test for the presence of specific enzymes can help confirm diagnosis. Other tests, such as urine testing (excess mucopolysaccharides are excreted in the urine), chromosome analysis, and cell or tissue culture (to see if cells are producing certain enzymes) may also be used. Prenatal diagnosis using amniocentesis or chorionic villus sampling can verify if a fetus carries one of the mutated genes that cause mucopolysaccharidosis.
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Treatment options vary by the type of mucopolysaccharidosis, but all involve a combination of therapies. Affected individuals may need to use wheelchairs or other mobility aids, and a number of complications are common. These include problems with the musculoskeletal system, such as bone fractures and contractures, heart valve disease, and joint pain. Many people with these diseases have vision loss due to accumulation of glycosaminoglycans in the cornea and retina. Some types of mucopolysaccharidosis can lead to the buildup of fluid in the brain (hydrocephalus), which can put pressure on brain tissues and lead to a variety of symptoms. In some cases, a surgical procedure called shunting can relieve the fluid buildup.
Affected individuals with milder forms of the condition can often live into adulthood. They may have cognitive impairment or developmental delay, and they may have severe behavioral problems. Several forms of mucopolysaccharidosis are associated with hearing loss, which can be either conductive (from pressure behind the eardrum) or neurosensory (from damage to tiny hairs that detect sound in the inner ear).
Hematopoietic stem cell transplantation can improve the health of patients with these rare conditions by correcting their enzyme deficiency through hematopoietic progenitor cells that are removed from the patient and injected back into his or her body. However, this procedure is only available at specialized centers that have experience treating patients with these disorders.
