Mucopolysaccharidoses

Mucopolysaccharidoses

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Mucopolysaccharidoses is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • MPS
  • MPS Disorder

Disorder Subdivisions

  • MPS I H (Hurler Disease)
  • MPS IV A and B (Morquio Syndrome)
  • MPS I S (Scheie Syndrome)
  • MPS III A, B, C, and D (Sanfillipo Syndrome)
  • MPS 1 H/S (Hurler/Scheie Syndrome)
  • MPS VII (Sly Syndrome)
  • MPS II-(Hunter Syndrome)
  • MPS VI (Maroteaux-Lamy Syndrome)
  • MPS IX (Hyaluronidase Deficiency)

General Discussion

The mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage disorders. Lysosomes function as the primary digestive units within cells. Enzymes within lysosomes break down or digest particular nutrients, such as certain carbohydrates and fats. In individuals with MPS disorders, deficiency or malfunction of specific lysosomal enzymes leads to an abnormal accumulation of certain complex carbohydrates (mucopolysaccharides or glycosaminoglycans) in the arteries, skeleton, eyes, joints, ears, skin, and/or teeth. These accumulations may also be found in the respiratory system, liver, spleen, central nervous system, blood, and bone marrow. This accumulation eventually causes progressive damage to cells, tissues, and various organ systems of the body. There are several different types and subtypes of mucopolysaccharidosis. These disorders, with one exception, are inherited as autosomal recessive traits.

Symptoms

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. 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.



Disorder 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 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 to 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 occur.



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, 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 case to case. Individuals may have normal intelligence or mild to moderate 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).



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.

Causes

All of the MPS disorders result from deficiency or malfunction of a specific lysosomal enzyme necessary in the breaking down of dermatan sulfate, heparan sulfate, or keratan sulfate, either alone or together. Failure to breakdown these mucopolysaccharides results in their accumulation in cells, tissues and organs throughout the body. All of these disorders are inherited as autosomal recessive traits except for Hunter syndrome, which is an X-linked recessive trait.



Genetic diseases are determined by two genes, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.



X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is "turned off" and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is turned off. Males have one X chromosome and if they inherit an X chromosome that contains a disease gene, they will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. Males cannot pass an X-linked gene to their sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% to have a son affected with the disease, and a 25% chance to have an unaffected son.

Affected Populations

The prevalence of all forms of mucopolysaccharidosis is estimated to be one in 25,000 births. However, because mucopolysaccharidoses, especially the milder forms of the diseases, often go unrecognized, these disorders are under-diagnosed or misdiagnosed, making it difficult to determine their true frequency in the general population.



Estimates for the specific types of mucopolysaccharidosis range from: one in 100,000 for Hurler syndrome; one in 500,000 for Scheie syndrome; one in 115,000 for Hurler-Scheie syndrome; one in 70,000 for Sanfilippo syndrome; one in 200,000 for Morquio syndrome; and fewer than one in 250,000 in Sly syndrome. Hunter syndrome occurs predominantly in males. In extremely rare cases, affected females have been reported. The incidence of Hunter syndrome is estimated at one in 100,000-150,000 male births.



More than 40 distinct lysosomal storage diseases have been identified.

Standard Therapies

Diagnosis

A diagnosis of a mucopolysaccharidosis disorder is made based upon a thorough clinical evaluation, identification of characteristic findings (e.g., coarse facial features, skeletal malformations, hepatosplenomegaly), and a variety of specialized tests including urine analysis to detect excessive levels of mucopolysaccharides. Tests known as enzyme assays may be performed to detect deficient levels of lysosomal enzymes in cells of the body.



Prenatal diagnosis is possible through the use of amniocentesis and chorionic villus sampling. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and studied. During CVS, tissue samples are removed from a portion of the placenta and specialized enzyme tests (assays) and DNA studies may be performed. Studies performed on these fluid or tissue samples can reveal deficiency or reduced activity of specific lysosomal enzymes.

Newborn screening pilot programs are currently underway to determine if MPS I and II can be detected in the newborn period. After an abnormal newborn screening result, it would be necessary to follow up with a definitive diagnosis by enzyme assay.



Management

The U.S. Food and Drug Administration (FDA) has approved (June 2005) galsulfase (Naglazyme) for the treatment of MPS VI, also known as Maroteaux-Lamy syndrome. Naglazyme, an orphan drug, is a product of BioMarin Pharmaceutical Inc.



The FDA has approved laronidase (Aldurazyme) as a treatment for MPS I (April 2003). Specifically, this enzyme replacement therapy is approved for treating patients with the Hurler and Hurler-Scheie forms of MPS I and those with the Scheie form who exhibit moderate to severe symptoms. Aldurazyme is manufactured by BioMarin Pharmaceutical Inc. and the Genzyme Corporation. It is the first treatment approved specifically for MPS I. For information about Aldurazyme, contact:



BioMarin Pharmaceutical Inc.

105 Digital Drive

Novato, CA 94949

Telephone: (415) 506-6700

Fax: (415) 382-7889

Patient Information: (415) 506-6100



Genzyme Corporation

500 Kendall Street

Cambridge, MA 02142

Telephone: (617) 252-7500

Fax: (617) 252-7600



The FDA has also approved idursulfase (Elaprase) for MPS II (July 2006) and for galsidase (Ngalazyme) for MPS VI (May 2005). Elaprase is manufactured by Shire Pharmaceuticals and Naglazyme by BioMarin Pharmaceutical Inc.

For information about Elaprase, contact:

Shire Human Genetic Therapies

700 Main Street

Cambridge Massachusetts 02139

Phone: 617-349-0200

Fax: 617-613-4004



Otherwise, treatment for the various forms of mucopolysaccharidosis is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, specialists who assess and treat heart problems (cardiologists), specialists who assess and treat hearing problems (audiologists), specialists who assess and treat eye problems (ophthalmologists), specialists who assess and treat skeletal problems (orthopedists), and other healthcare professionals may need to systematically and comprehensively plan an affected child's treatment.



Surgery may be used to treat a variety of symptoms associated with mucopolysaccharidosis, including carpal tunnel syndrome, skeletal malformations, and hernias. Corneal transplantation has been performed with mixed results. Physical therapy and exercise may improve joint stiffness. Hydrocephalus may be treated by the insertion of a tube (shunt) to drain excess cerebrospinal fluid (CSF) away from the brain and into another part of the body where the CSF can be absorbed. Heart valve replacement may be necessary in some cases.



Genetic counseling will be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government Web site.



For information about clinical trials conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

E-mail: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com



Since prenatal diagnosis is possible through the use of amniocentesis and tissue sampling of the embryo, new diagnostic interventions are being developed. Experimental treatments that 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.



Bone marrow transplantation as a way to replace defective enzymes has been studied as a treatment for individuals with mucopolysaccharidosis. The effectiveness of BMT has varied greatly. Physical characteristics may improve, such as cloudy corneas may become clear, the size of an abnormally enlarged liver and spleen may decrease, and mucopolysaccharide levels may drop. Skeletal malformations are unaffected, however. The effect on neurological symptoms varies considerably. Because BMT is a procedure that carries significant risks, it should only be considered in selected cases.



Enzyme replacement therapy for MPS III (A), San Filippo syndrome Type A and for MPS IV (Morquio syndrome) is currently under investigation.



Gene therapy is under study as a possible treatment for mucopolysaccharidosis. More studies are needed to determine the safety and effectiveness of gene therapy as a possible treatment for Hurler syndrome and other mucopolysaccharidoses.

References

TEXTBOOKS

Fauci AS, et al., eds. Harrison's Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:2169-76.



Behrman RE, ed. Nelson Textbook of Pediatrics, 15th ed. Philadelphia, PA: W.B. Saunders Company; 1996:398-403.



Scriver CR, et al., eds. The Metabolic and Molecular Basis of Inherited Disease. 7th Ed. New York, NY; McGraw-Hill Companies, Inc; 1995:2465-85.



Beighton P, ed. Mckusick's Heritable Disorders of Connective Tissue. 5th ed. St. Louis, MO: Mosby-Year Book, Inc; 1993:1118-9.



JOURNAL ARTICLES

Desnick RJ. Enzyme replacement and enhancement therapies for lysosomal diseases. J. Inherit Metab Dis. 2004;27:385-410.



Wraith JE, Clarke LA, Beck M, et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr. 2004;144:581-88.



Staba SL, et al. Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. N Engl J Med. 2004;350:1960-69.



Muenzer J and Fisher A. Advances in the Treatment of Mucopolysaccharidosis Type I. New Engl J Med. 2004;350:1932-34.



Malm G, et al. Mucopolysaccharidoses. New therapeutic possibilities increase the need of early diagnosis. Lakartidningen. 2002;99:1804-9.



Kakkis ED. Enzyme replacement therapy for the mucopolysaccharides storage disorders. Expert Opin Investig Drugs. 2002;11:675-85.



Wraith JE. Enzyme replacement therapy in mucopolysaccharidosis type I: progress and emerging difficulties. J Inherit Metab Dis. 2001;24:245-50.



Kakkis ED, et al., Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med. 2001;344:182-8.



Eto Y, Ohashi T. Gene therapy/cell therapy for lysosomal storage disease. J Inherit Metab Dis. 2000;293-8.



Triggs-Raine B, et al. Mutations in HYAL1, a member of a tandemly distributed multigene family encoding disparate hyaluronidase activities, cause a newly described lysosomal disorder, mucopolysaccharidosis IX. Proc Natl Acad Sci USA. 1999;95:6296-300.



Natowicz MR, et al. Clinical biochemical manifestations of hyaluronidase deficiency. N Engl J Med. 1996;335:1029-33.



Herrick IA, et al. The mucopolysaccharidoses and anaesthesia: a report of clinical experience. Can J Anaesth. 1988;35:67-73.



Sjogren P, et al. Mucopolysaccharidoses and anaesthetic risks. Acta Anaesthesiol Scand. 1987;31:214-8.



Caruso RC, et al. Electroretinographic findings in the mucopolysaccharidoses. Ophthalmology. 1986;93::1612-6.



FROM THE INTERNET

Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Alpha-L-Iduronidase; IDUA. Entry No: 252800. Last Edited March 5, 2009. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed October 13, 2011.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Mucopolysaccharidosis Type II. Entry No: 309900. Last Edited April 7, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed October 13, 2011.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Mucopolysaccharidosis Type III. Entry No: 252900. Last Updated March 21, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed October 13, 2011.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Mucopolysaccharidosis Type IIIB. Entry No: 252920. Last Edited May 12, 2008. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed October 13, 2011.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Mucopolysaccharidosis Type IIIC. Entry No: 252930. Last Edited September 21, 2009. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed October 13, 2011.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Mucopolysaccharidosis Type IIID. Entry No: 252940. Last Edited March 19, 2010. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed October 13, 2011.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Mucopolysaccharidosis Type IVA. Entry No: 253000. Last Edited January 10, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed October 13, 2011.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Mucopolysaccharidosis Type IVB. Entry No: 253010. Last Edited January 10, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed October 13, 2011.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Mucopolysaccharidosis Type VI. Entry No: 253200. Last Edited November 17, 2009. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed October 13, 2011.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Mucopolysaccharidosis Type VII. Entry No: 253220. Last Edited June 8, 2011. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed October 13, 2011.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Mucopolysaccharidosis Type VIII. Entry No: 253230. Last Edited January 29, 2009. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed October 13, 2011.



Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Mucopolysaccharidosis Type IX. Entry No: 601492. Last Edited December 8, 2010. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed October 13, 2011.

Resources

March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



National MPS Society, Inc.

PO Box 14686

Durham, NC 27709

Tel: (919)806-0101

Fax: (919)806-2055

Tel: (877)677-1001

Email: info@mpssociety.org

Internet: http://www.mpssociety.org



NIH/National Institute of Diabetes, Digestive & Kidney Diseases

Office of Communications & Public Liaison

Bldg 31, Rm 9A06

31 Center Drive, MSC 2560

Bethesda, MD 20892-2560

Tel: (301)496-3583

Email: NDDIC@info.niddk.nih.gov

Internet: http://www2.niddk.nih.gov/



NIH/National Institute of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

Tel: (301)496-5751

Fax: (301)402-2186

Tel: (800)352-9424

TDD: (301)468-5981

Internet: http://www.ninds.nih.gov/



Society for Mucopolysaccharide Diseases

MPS House

Repton Place

White Lion Road

Amersham

Buckinghamshire, HP7 9LP

United Kingdom

Tel: 08453899901

Fax: 08453899902

Email: mps@mpssociety.co.uk

Internet: http://www.mpssociety.co.uk



Canadian Society for Mucopolysaccharide and Related Diseases, Inc.

PO Box 30034

RPO Parkgate

North Vancouver

British Columbia, V7H 2Y8

Canada

Tel: 6049245130

Fax: 6049245131

Tel: 8006671846

Email: info@mpssociety.ca

Internet: http://www.mpssociety.ca



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



Let Them Hear Foundation

1900 University Avenue, Suite 101

East Palo Alto, CA 94303

Tel: (650)462-3174

Fax: (650)462-3144

Email: info@letthemhear.org

Internet: http://www.letthemhear.org



Hide & Seek Foundation for Lysosomal Disease Research

6475 East Pacific Coast Highway Suite 466

Long Beach, CA 90803

Tel: (877)621-1122

Fax: (866)215-8850

Email: info@hideandseek.org

Internet: http://www.hideandseek.org



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use . How this information was developed to help you make better health decisions.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.