Individuals with MPS disorders share many similar symptoms such as multiple organ involvement, distinctive “coarse” facial features, and abnormalities of the skeleton especially joint problems. Additional findings include short stature, heart abnormalities, breathing irregularities, liver and spleen enlargement (hepatosplenomegaly), and/or neurological abnormalities. The severity of the different MPS disorders varies greatly among affected individuals, even among those with the same type of MPS and even among individuals of the same family.
In most cases of MPS, affected infants appear normal at birth and symptoms become apparent around the age of one or two, however, in MPS VII, approximately 40% of pregnancies with an affected baby are complicated by a condition called non-immune hydrops fetalis that may be detected on routine ultrasound examination. Initial symptoms may include frequent colds, runny nose, infections, growth delays, or mild developmental delays. Mild forms of these disorders may not become apparent until childhood or adolescence. In most cases, the mucopolysaccharidoses are chronic, progressive disorders and, depending upon the type of MPS and severity, affected individuals may experience a decline in physical and mental function, sometimes resulting in life-threatening complications.
There are different types of mucopolysaccharides that are not broken down due to enzyme malfunction or deficiency. Specifically, the mucopolysaccharides known as dermatan sulfate, heparan sulfate, or keratan sulfate may be involved alone or in some combination.
MPS Subdivisions: Hurler syndrome (mucopolysaccharidosis type 1-H; MPS 1-H) is the most severe form of mucopolysaccharidosis. It is characterized by a deficiency of the enzyme alpha-L-iduronidase, which results in an accumulation of dermatan and heparan sulfates. Symptoms of the disorder first become evident at six months to two years of age. Affected infants may experience developmental delays, recurrent urinary and upper respiratory tract infections, noisy breathing and persistent nasal discharge. Additional physical problems may include clouding of the cornea of the eye, an unusually large tongue, severe deformity of the spine, and joint stiffness. Mental development begins to regress at about the age of two.
Scheie syndrome (mucopolysaccharidosis type I-S; MPS 1-S) is the mildest form of mucopolysaccharidosis. As in Hurler syndrome, individuals with Scheie syndrome have a deficiency of the enzyme alpha-L-iduronidase. However, in Scheie syndrome the deficiency is specific for accumulation of dermatan sulfate. Individuals with Scheie syndrome have normal intelligence, height, and life expectancy. Symptoms include stiff joints, carpal tunnel syndrome, backward flow of blood into the heart (aortic regurgitation), and clouding of the cornea that may result in the loss of visual acuity. The onset of symptoms in individuals with Scheie syndrome usually occurs around the age of five.
Hurler-Scheie syndrome (mucopolysaccharidosis type I-H/S; MPS-IH/S) is an extremely rare disorder that refers to individuals who have a less severe form of Hurler syndrome, but a more severe form than Scheie syndrome. Like Scheie syndrome, affected individuals have a deficiency of the alpha-L-iduronidase specific for accumulation of dermatan sulfate. Hurler-Scheie syndrome is not as severe as Hurler syndrome, but more severe than Scheie syndrome. Affected individuals may develop coarse facial features, joint stiffness, short stature, clouding of the corneas, abnormally enlarged liver and/spleen (hepatosplenomegaly), and skeletal and cardiac abnormalities. Intelligence may be normal or mild to moderate intellectual disability may develop. Symptoms usually become apparent between three and six years of age.
Hunter syndrome (mucopolysaccharidosis type II; MPS II) is the only type of MPS disorder inherited as an X-linked trait. Initial symptoms and findings associated with Hunter syndrome usually become apparent between ages two to four years. Such abnormalities may include progressive growth delays, resulting in short stature; joint stiffness, with associated restriction of movements; and coarsening of facial features, including thickening of the lips, tongue, and nostrils. Affected children may also have an abnormally large head (macrocephaly), a short neck and broad chest, delayed tooth eruption, progressive hearing loss, and enlargement of the liver and spleen (hepatosplenomegaly). Accumulation of heparin sulfate may occur. Two relatively distinct clinical forms of Hunter syndrome have been recognized. In the mild form of the disease (MPS IIB), intelligence may be normal or only slightly impaired. However, in the more severe form (MPS IIA), profound intellectual disability may become apparent by late childhood. In addition, slower disease progression tends to occur in those with the mild form of the disorder.
Sanfilippo syndrome (mucopolysaccharidosis type III; MPS III) has four subtypes (A, B, C, and D) that are distinguished by four different enzyme deficiencies. Initial symptoms of the four types of Sanfilippo syndrome include hyperactivity, sleep disorders, and delays in attaining developmental milestones (e.g., crawling and walking). All forms of Sanfilippo syndrome are characterized by varying degrees of intellectual disability, progressive loss of previously acquired skills (e.g., language), and hearing loss. Affected individuals may experience Seizures, unsteady gait, and aggressive behavior. Affected individuals may eventually lose the ability to walk. Accumulation of heparan sulfate may occur.
Morquio syndrome (mucopolysaccharidosis type IV; MPS IV) exists in two forms (Morquio syndromes A and B) and occurs because of a deficiency of the enzyme N-acetyl-galactosamine-6-sulfatase and beta-galactosidase, respectively, resulting in accumulation of keratan and chondroitin sulfate in type A and keratan sulfate in type B. A deficiency of either enzyme leads to the accumulation of mucopolysaccharides in the body, abnormal skeletal development, and additional symptoms. In most cases, individuals with Morquio syndrome have normal intelligence. The clinical features of MPS IV-B are usually fewer and milder than those associated with MPS IV-A. Symptoms may include growth retardation, a prominent lower face, an abnormally short neck, knees that are abnormally close together (knock knees or genu valgum), flat feet, abnormal sideways and front-to-back or side-to-side curvature of the spine (kyphoscoliosis), abnormal development of the growing ends of the long bones (epiphyses), and/or a prominent breast bone (pectus carinatum). In some cases, hearing loss, Weakness of the legs, and/or additional abnormalities also occurs.
Mucopolysaccharidosis type V is the former designation for Scheie syndrome. However when it was discovered that both Hurler and Scheie syndromes occur due to a deficiency of the same enzyme, Scheie syndrome was reclassified as a subtype of mucopolysaccharidosis type I.
Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI; MPS VI) is characterized by a deficiency of the enzyme N-acetylgalactosamine-4-sulfatase, resulting in accumulation of dermatan sulfate. This form of MPS varies greatly among affected individuals. Some affected individuals only experience a few mild symptoms, other develop a more severe form of the disorder. Possible symptoms of Maroteaux-Lamy syndrome include coarse facial features, umbilical hernia, a prominent breast bone (pectus carinatum), joint contractures, clouding of the corneas, and an abnormal enlargement of the liver and/or spleen (heptasplenomegaly). Skeletal malformations and heart disease may occur in individuals with this form of MPS. In most cases, intelligence is normal.
Sly syndrome (mucopolysaccharidosis type VII; MPS VII) is characterized by a deficiency of the enzyme beta-glucuronidase, resulting in the accumulation of three glycosaminoglycans: dermatan sulfate, heparan sulfate and chondroitin sulfate. The symptoms may vary greatly from person to person. Individuals may have normal intelligence or mild to severe intellectual disability. Some skeletal abnormalities are often present. Hernias, clouding of the corneas, excessive accumulation of cerebrospinal fluid in the skull (hydrocephalus), short stature, heart disease, and coarse facial features have also been reported. In rare cases, some newborn infants with Sly syndrome may experience abnormal accumulation of fluid in various tissues of the body (hydrops fetalis). MPS VII is currently in clinical trial.
DiFerrante syndrome (mucopolysaccharidosis VIII; MPS VIII) is an obsolete term for a form of MPS described in a single individual with clinical and biochemical features of Morquio and Sanfilippo syndromes. The disorder had been reported to be due to a deficiency of glucosamine-6-sulfate sulfatase. Subsequently, this disorder was called MPS VIII (DiFerrante syndrome). Dr. DiFerrante later found that the enzyme was normal in his patient, and the disorder had been misdiagnosed. Therefore, DiFerrante syndrome is not a valid medical disorder.
Hyaluronidase deficiency (mucopolysaccharidosis IX; MPS IX) is an extremely rare form of MPS characterized by a deficiency of the enzyme hyaluronidase, which is needed to breakdown the mucopolysaccharides known as hyaluronan (hyaluronic acid). This form of MPS was first described in 1996. Symptoms may include mild short stature, cysts, frequent ear infections, cleft palate, and the development of soft-tissue masses. However, more cases of this form of MPS must be identified before a clear clinical picture can be established.