Mucopolysaccharidosis (MPS) is a group of related lysosomal storage diseases. Lysosomes are compartments in cells that break down molecules and remove waste products from cells. Normally, 11 different enzymes in the lysosomes break down sugars called glycosaminoglycans, also known as mucopolysaccharides. In MPS, glycosaminoglycans are not broken down because of a deficiency in one of the 11 enzymes. As a result, the glycosaminoglycans accumulate in the cells and cause tissue damage.
Different types of MPS are classified by the enzymes that are absent or deficient. To date, seven types of MPS have been reported, MPS I, II, III, IV, VI, VII, and IX.
All types of MPS are inherited and share very similar physical symptoms. The physical symptoms may include thickening of lips and skin, enlarged tongue and mouth, abnormal bone size and shape, joint pain and stiffness, and short stature. Neurological symptoms are present in some types of MPS and may vary in severity.
It is estimated that in the United States, one in 25,000 births are affected by some form of MPS. MPS III, also called Sanfilippo syndrome, is one of the more common types, while MPS VII is very rare. Lifespan of a patient with MPS varies depending on the severity and type of disease but it is possible for a person with a mild form of MPS to live into adulthood.
There is currently no known cure for MPS. Treatment aims to relieve and manage symptoms in order to improve and prolong life. Physical therapy and surgery may be useful for correcting abnormalities. Therapies that aim to replace the deficient enzymes may help improve pain and neurological symptoms.
Acetyl-CoA:alpha-glucosaminide acetyltransferase, alpha-L-iduronidase, alpha-N-acetylglucosaminidase, autosomal recessive disorders, beta-galactosidase, beta-glucuronidase, gargoylism, glycosaminoglycan, heparan sulfate, heparin sulfate, Hunter syndrome, Hurler syndrome, Hurler-Scheme syndrome, hyaluronidase deficiency, iduronate sulfatase, inborn errors of carbohydrate metabolism, lysosomal storage diseases, Maroteaux-Lamy syndrome, Morquio syndrome, MPS, mucopolysaccharidosis, N-acetylgalactosamine 4-sulfatase, N-acetylgalactosamine 6-sulfatase, N-acetylglucosamine 6-sulfatase, Sanfilippo syndrome, Scheie syndrome, Sly syndrome, X-linked disorders.
types of the disease
MPS I: There are three subtypes of MPS I, and they are MPS I H, MPS I S, and MPS I H-S, which are also known as Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome, respectively. All subtypes of MPS I affect the enzyme alpha-L-iduronidase and are diagnosed based on the severity of symptoms. A deficiency in alpha-L-iduronidase leads to an increased level in the glycosaminoglycans dermatan sulfate and heparin sulfate. These glycosaminoglycans normally have a role in processes involving the development and regulation of blood vessels, heart valves, connective tissue, skin, and lungs.
MPS I H is the most severe type of MPS I. Average life expectancy is 10 years and symptoms begin during the first years of life. Hernias, airway complications, and cardiac abnormalities are common features.
MPS I S is the least severe form of MPS I with patients living well into adulthood. The mental capacity of MPS I S is often normal with corneal clouding being the major symptom.
MPS I H-S is a combination of the typical MPS I H and MPS I S. Life expectancy for this type is longer than that of MPS I H.
MPS II: There are two subtypes of MPS II: MPS II A and B. These disorders are also known as Hunter syndrome A or B. All types of MPS II affect the enzyme iduronate sulfatase. A deficiency in iduronate sulfatase will result in an increased level of the glycosaminoglycans chondroitin sulfate B and heparitin sulfate. These glycosaminoglycans help to form and regulate connective tissue, blood vessels, cartilage, and the lungs. This is the only form of MPS that is X-linked dominant. The two subtypes are diagnosed as A or B based upon the severity of symptoms.
MPS II A is the most severe form with features similar to MPS I H. Distinguishing features include white skin lesions and hydrocephalus (accumulation of fluid around the brain). MPS II A typically has progressive intellectual disability (formerly mental retardation) and physical disabilities. Life expectancy is about 15 years.
MPS II B has a slower progression and does not affect mental development. Many patients with MPS II B often live into adulthood.
MPS III: This type is also known as Sanfilippo syndrome and has the subtypes A, B, C, and D. Diagnosis is based on a deficiency of one of the enzymes that breaks down heparan sulfate. Type A is a deficiency of heparan N-sulfatase, B is a deficiency of alpha-N-acetylglucosaminidase, C is a deficiency of acetyl-CoA alpha-glucosaminide acetyltransferase, and D is a deficiency of N-acetylglucosamine 6-sulfatase. A buildup of heparan sulfate often results in central nervous system deterioration but may also disrupt normal bone, joint, lung, and heart function. Typical physical symptoms of all MPS types are present. These may include thickened lips and skin, enlarged tongue and mouth, abnormal bone size and shape, joint pain and stiffness, and short stature. MPS III is characterized by severe neurological symptoms.
There is little clinical distinction between the different types of MPS III, with the exception of type A, which is more severe and more quickly progressing. Onset of symptoms generally occurs between the ages of two to six years with an average life expectancy of 20 to 30 years depending on the disease severity. Intellect and behavioral functioning are largely impaired. Progressive hearing and vision loss may also occur.
MPS IV: Also known as Morquio syndrome, MPS IV also has subtypes A and B. In MPS IV, the enzymes that break down keratin sulfate are deficient. The two subtypes are distinguished by the specific enzyme that is deficient. Type A is caused by a deficiency in the enzyme N-acetylgalactosamine 6-sulfatase and type B is caused by a deficiency of beta-galactosidase. The two types usually have similar symptoms and disease progression. The glycosaminoglycan keratin sulfate is normally found in bone, cartilage, and the cornea. Therefore, the major effects of MPS IV are corneal clouding and bone changes that may lead to abnormal neurological and organ function.
MPS VI: Also known as Maroteaux-Lamy syndrome, this type of MPS is caused by a deficiency in the enzyme N-acetylgalactosamine 4-sulfatase. A deficiency of this enzyme results in an increase in the glycosaminoglycan chondroitin sulfate. Chondroitin sulfate,
like many other glycosaminoglycans, has developmental and regulatory effects on bone, cartilage, the cornea, connective tissue, blood vessels, and heart cells.
Mental development is often normal and the physical symptoms are similar to MPS II. The physical symptoms may include thickened lips and skin, enlarged tongue and mouth, abnormal bone size and shape, joint pain and stiffness, corneal clouding, and short stature. Heart abnormalities like valve defects, thickening and stiffening of the heart wall, and narrowing of blood vessels are also common in MPS VI.
MPS VII: Also known as Sly syndrome, MPS VII involves a deficiency of the enzyme beta-glucuronidase. A deficiency of beta-glucuronidase leads to an increase in glucuronic acid-containing glycosaminoglycans. Glucuronic acid is found in chondroitin, dermata, keratin, and heparan sulfate.
This is one of the least common forms of MPS, with symptoms that consist of the typical physical and neurological presentation seen in the other types of MPS. The physical symptoms may include thickened lips and skin, enlarged tongue and mouth, abnormal bone size and shape, joint pain and stiffness, corneal clouding, and short stature. Decreased intellectual capacity, hyperactivity, delirium, and aggressive behavior are common neurological signs.
MPS IX: MPS IX is caused by a deficiency of the enzyme hyaluronidase. Hyaluronidase is responsible for the breakdown of the glycosaminoglycan hyaluronan. Hyaluronan is a major component of skin, connective tissue, cartilage, and brain development. There are very limited reported cases of MPS IX in the scientific literature.