$Unique_ID{BRK04013} $Pretitle{} $Title{Mucopolysaccharidosis} $Subject{Mucopolysaccharidosis MPS MPS Disorder MPS I H (Hurler Disease) MPS I S (Scheie Syndrome) MPS I H/S (Hurler/Scheie Syndrome) MPS II-XR, severe (Hunter Syndrome) MPS II-XR, mild (Hunter Syndrome) MPS II-AR, autosomal (Hunter Syndrome) MPS III A, B, C, and D (Sanfilippo A) MPS IV A and B (Morquio A) MPS V (No longer used) MPS VI, severe, intermediate, mild (Maroteaux-Lamy) MPS VII (Sly Syndrome) MPS VIII (No longer used) Pseudo-Hurler Polydystrophy Ganglioside Sialidase Deficiency I-Cell Disease } $Volume{} $Log{} Copyright (C) 1989 National Organization for Rare Disorders, Inc. 688: Mucopolysaccharidosis ** IMPORTANT ** It is possible that the main title of the article (Mucopolysaccharidosis) is not the name you expected. Please check the SYNONYM listing to find the alternate names and disorder subdivisions covered by this article. Synonyms MPS MPS Disorder Disorder Subdivisions: MPS I H (Hurler Disease) MPS I S (Scheie Syndrome) MPS I H/S (Hurler/Scheie Syndrome) MPS II-XR, severe (Hunter Syndrome) MPS II-XR, mild (Hunter Syndrome) MPS II-AR, autosomal (Hunter Syndrome) MPS III A, B, C, and D (Sanfilippo A) MPS IV A and B (Morquio A) MPS V (No longer used) MPS VI, severe, intermediate, mild (Maroteaux-Lamy) MPS VII (Sly Syndrome) MPS VIII (No longer used) Information on the following diseases can be found in the Related Disorders section of this report: Pseudo-Hurler Polydystrophy Ganglioside Sialidase Deficiency I-Cell Disease General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. The Mucopolysaccharidoses are a group of hereditary diseases of lysosomal storage. They are characterized by deposits of mucopolysaccharides in the arteries, skeleton, eyes, joints, ears, skin and teeth. These deposits may also be found in the respiratory system, liver, spleen, central nervous system, blood cells and bone marrow. Symptoms MPS consists of a group of hereditary diseases. These diseases are characterized by an abnormal accumulation of mucopolysaccharides, especially in the cartilage and bone tissue. In general these disorders are progressive and usually disabling. The child may appear normal at birth and around the age of one begin to show signs of both growth and mental retardation. After the age of three or four growth may seem to cease. This growth retardation occurs in all of the MPS disorders except the Scheie Syndrome. Many patients develop serious vision and hearing problems. Stiff joints occur in all but the Morquio Syndrome. Excessive hairiness (hirsutism), dwarfism, and heart problems (especially Angina Pectoris) are common features of most of the syndromes. Breathing problems may occur as a result of the narrowing of the airways due to skeletal deformities. The liver and spleen are enlarged in most MPS patients. The central nervous system and brain may also be affected. Disorder Subdivisions: Mucopolysaccharidoses I in the severe form is Hurler Syndrome. It is characterized by high concentrations of dermatan and heparan sulfates, in the urine. Symptoms of the disorder first become evident at six months to two years of age. There is developmental delay, recurrent urinary and upper respiratory tract infections, noisy breathing and a persistent nasal discharge. Swelling of the head (hydrocephalus) is common after the age of two. Other physical problems may include clouding of the cornea of the eye, an unusually large tongue, misaligned teeth, severe deformity of the spine, joint stiffness and clawlike hands. Mental development begins to regress at about the age of two. (For more information on this disorder choose "Hurler" as your search term in the Rare Disease Database.) Scheie Syndrome is the milder form of MPS I. The patient has a normal intelligence, stature and life expectancy, but suffers from physical symptoms such as stiff joints, clouding of the cornea, and the backward flow of blood into the heart (aortic regurgitation). The onset of symptoms in patients with Scheie Syndrome usually occurs after the age of five years. However, diagnosis is commonly delayed to between ten to twenty years of age. (For more information on this disorder choose "Hurler" as your search term in the Rare Disease Database.) Hurler-Scheie Syndrome is an intermediate form of MPS I and is characterized by normal intelligence but progressive physical involvement which is milder than Hurler Syndrome. Corneal clouding, joint stiffness, deafness and valvular heart disease can develop by the early to mid-teens, causing significant impairment. (For more information on this disorder choose "Hurler" as your search term in the Rare Disease Database.) Mucopolysaccharidoses II, Hunter Syndrome, is the most prevalent form of MPS. In the severe form, physical and mental development reach a peak at two to four years with subsequent deterioration. Recurrent urinary and upper respiratory tract infections, a chronic runny nose, liver and spleen enlargement, joint stiffness and growth failure commonly occur. There is coarsening of the facial features with thickening of the nostrils, lips and tongue. Swelling of the head (hydrocephalus) is commonly found in this form of Hunter Syndrome as is thicker than normal skin, short neck, widely spaced teeth, and hearing loss of varying degree. Skin lesions on the arm or the posterior chest wall, extra-high arched feet and diarrhea may also occur. (For more information on this disorder choose "Hunter" as your search term in the Rare Disease Database.) The milder form of Hunter MPS II is characterized by less severe physical deterioration and normal intelligence. Complications of the mild form of the disorder may include heart disease, hearing impairment, reduced circulation and joint stiffness in the hands. (For more information on this disorder choose "Hunter" as your search term in the Rare Disease.) The autosomal form of Hunter MPS II can have a combination of the symptoms of both the severe and mild forms of Hunter Syndrome. (Choose "Hunter" as your search term on the Rare Disease Database.) Mucopolysaccharidosis III is titled Sanfilippo Syndrome and is characterized by progressive mental retardation and the excretion of heparan sulfate in the urine. There is variability in the degree of mental retardation. The patient will usually begin to show hyperactivity and sleep disorders around the age of two or three. The child may be able to start school but will usually become a "behavior problem" and loose the ability to speak. The excretion of heparan sulfate is the strongest evidence of MPS III. MPS III A, B, C, and D range in severity from A the most severe to D the least severe. The means of classification of the various types of MPS III rests in the lack of specific enzymes in the process of eliminating heparan sulfate. Type A lacks the enzyme heparan N-sulfatase. Type B lacks the enzyme acetylated glucosamines initially present in heparan sulfate. Type C lacks the enzyme N-acetyltransferase reaction. Type D lacks the enzyme sulfatase reaction. (For more information on this disorder choose "Sanfilippo" as you search term in the Rare Disease Database.) Mucopolysaccharidosis IV is characterized by the excretion of keratan sulfate in the urine. This syndrome is also known as the Morquio Syndrome. The developmental abnormalities may be detected as early an eighteen months to two years of age. The skeletal abnormalities are milder in Morquio B than in Morquio A. These may include an enlarged head, a broad mouth, prominent cheekbones, an unusually small nose, widely spaced and thinly enameled teeth, and widely separated eyes with corneal clouding. Later, patients tend to develop abnormally short necks, short barrel chests, disproportionately long arms, enlarged and possibly hyperextensible wrists, stubby hands and "knock knees". Together with the misaligned knees and knobby joints, the child may be "pigeon-toed", causing a wobbly gait. There may also be enlargement of the liver, curvature of the spine, heart problems and hearing loss. The intelligence of the patient is usually normal. (For more information on this disorder choose "Morquio" as your search term in the Rare Disease Database.) Mucopolysaccharidosis V, (The Scheie Syndrome) is now designated as MPS I because of the close relationship to the Hurler syndrome. (Choose "Hurler" as your search term in the Rare Disease Database.) Mucopolysaccharidosis VI, also known as Maroteaux-Lamy Syndrome, is classified by severe, mild and intermediate types. It is characterized by growth retardation beginning around two to three years of age. There is a coarsening of facial features and abnormalities in the bones of hands and spine creating a dwarflike appearance. Stiff joints, a hunched spine, prominent chestbone, and pain in the hip bone all tend to appear after the first four years. There may also be noisy and strained breathing, intermittent deafness and an enlarged liver and spleen. (For more information on this disorder choose "Maroteaux" as your search term in the Rare Disease Database.) Mucopolysaccharidosis VII is also called Sly Syndrome. It is characterized by an increased amount of dermatan sulfate and heparan sulfate in the urine. Sly Syndrome usually results in mental retardation. Other symptoms may include short stature and skeletal abnormalities such as joint contractures, dislocated hips, and spinal malformations. The liver and spleen may be enlarged, there may be hernias in the groin and navel areas and there may also be clouding of the cornea of the eye. This type of Mucopolysaccharidoses VII is very rare and affects less than twenty persons worldwide. (For more information on this disorder choose "Sly" as your search term in the Rare Disease Database.) Mucopolysaccharidoses VIII, DiFerrante Syndrome is not a valid disorder, and it is no longer used. Causes All of the MPS diseases result from deficiency of specific lysosomal enzymes involved in the breaking down of dermatan sulfate, heparan sulfate, or keratan sulfate, either alone or together. These mucopolysaccharides accumulate in tissues and organs and are also excreted in the urine. All of these diseases are inherited as autosomal recessive except for the Hunter Syndrome which is X-linked recessive. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will show no symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent, and will be genetically normal. X-linked recessive disorders are conditions which are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore, in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males only have one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a fifty percent risk of transmitting the carrier condition to their daughters, and a fifty percent risk of transmitting the disease to their sons. Affected Population All of the MPS disorders affect males and females in equal numbers with the exception of the Hunter Syndrome which affects only males. Related Disorders Symptoms of the following disorders can be similar to those of MPS. Comparisons may be useful for a differential diagnosis: Pseudo-Hurler Polydystrophy is an autosomal recessive inherited disorder, characterized by onset in childhood, painless joint stiffness, decreased mobility, short stature, some coarseness of the facial features, mild mental retardation, evidence of multiple defective bone formations and aortic valve (heart) disease. (For more information on this disorder, choose "Pseudo- Hurler" as your search term in the Rare Disease Database). Ganglioside Sialidase Deficiency is characterized by a deficiency in the enzyme ganglioside sialidase which causes abnormalities of connective tissue cells, defects of the cornea and retardation of physical and mental development. The first symptom usually is clouding of the eye's cornea. The development of physical and mental retardation usually begins after the child's first year of life. (For more information on this disorder, choose "Ganglioside" as your search term in the Rare Disease Database). I-Cell Disease begins very early in life. By the age of six months children have begun to show symptoms such as coarse facial features (e.g., as depressed nasal bridge), a long and narrow head, excessive hair growth, and a low forehead. They may also show severe skeletal changes including curvature of the spine, a lumbar hump, problems with their vertebra, widening of the ribs, and pointing of the long bones of the hands. Mental and physical retardation is common. Frequent respiratory infections and severe joint contractures occur as do opacities of the cornea of the eye. (For more information on this disorder, choose "I-Cell" as your search term in the Rare Disease Database). Therapies: Standard Treatment of all of the Mucopolysaccharidoses disorders is symptomatic and supportive. If hernias, joint contractures, hydrocephalus and eye problems occur, surgery to correct the problem may be indicated. Physical therapy may also be of benefit. Genetic counseling will be of benefit to families of patients with MPS disorders. Therapies: Investigational Since prenatal diagnosis is possible through the use of amniocentesis and tissue sampling of the embryo, new diagnostic interventions are being developed. Experimental treatments scientists are trying to develop include replacing defective enzymes via enzyme replacement therapy and/or bone marrow transplants. Scientific study of gene replacement in animal models raises the hope that gene replacement therapy may someday be made available to people with serious genetic disorders. This disease entry is based upon medical information available through August 1989. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Mucopolysaccharidoses, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 MPS (Mucopolysaccharidoses) Research Funding Center, Inc. 1215 Maxfield Road Hartland, MI 48029 (313) 363-4412 National MPS Society 17 Kramer Street Hicksville, NY 11801 (516) 931-6338 Society of MPS Diseases 30 Westwood Drive Little Chalfont, Bucks, England Society of Mucopolysaccharide Diseases, Inc. 382 Parkway Blvd. Flin Flon, Manitoba, Canada R8A OK4 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 For genetic information and genetic counseling referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References THE METABOLIC BASIS OF INHERITED DISEASE, 6th Ed.: Charles R. Scriver, et al., eds.; McGraw Hill, 1989. Pp. 1565-1588. THE MUCOPOLYSACCHARIDOSES AND ANAESTHESIA: A REPORT OF CLINICAL EXPERIENCE. I.A. Herrick, et al.; Can J Anaesth (January, 1988, issue 35 (1)). Pp. 67-73. MUCOPOLYSACCHARIDOSES AND ANAESTHETIC RISKS. P. Sjogren, et al.; Acta Anaesthesiol Scand (April, 1987, issue 31 (3) ). Pp. 214-218. ELECTRORETINOGRAPHIC FINDINGS IN THE MUCOPOLYSACCHARIDOSES. R.C. Caruso, et al.; Ophthalmology (December, 1986, issue 93 (12)). Pp. 1612-1616.