$Unique_ID{BRK03833} $Pretitle{} $Title{Hurler Syndrome} $Subject{Hurler Syndrome Mucopolysaccharidosis Type I MPS Disorder MPS I Gargoylism Hurler Disease Mucopolysaccharidosis I-H Scheie Syndrome Mucopolysaccharidosis I-S Hurler-Scheie Syndrome} $Volume{} $Log{} Copyright (C) 1986, 1987, 1988, 1990, 1991 National Organization for Rare Disorders, Inc. 284: Hurler Syndrome ** IMPORTANT ** It is possible the main title of the article (Hurler Syndrome) is not the name you expected. Please check the SYNONYMS listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Mucopolysaccharidosis Type I MPS Disorder MPS I Gargoylism DISORDER SUBDIVISIONS Hurler Disease, also known as Mucopolysaccharidosis I-H Scheie Syndrome, also known as Mucopolysaccharidosis I-S Hurler-Scheie Syndrome 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. Mucopolysaccharidoses (MPS Disorders), are a group of rare genetic disorders caused by the deficiency of one of ten specific lysosomal enzymes, resulting in an inability to metabolize complex carbohydrates (mucopolysaccharides) into simpler molecules. The accumulation of these large, undegraded mucopolysaccharides in the cells of the body causes a number of physical symptoms and abnormalities. Hurler Syndrome is a form of MPS. Symptoms There are three forms of Hurler Syndrome with varying severity. All are due to alpha-L-iduronidase deficiency. Infants with Hurler Syndrome usually appear normal at birth, but may have inguinal and umbilical hernias. The diagnosis of Hurler Syndrome is commonly made between 6 and 24 months of age when the patient may exhibit coarse facial features, clouding of the cornea, enlarged liver and spleen, a large tongue, skeletal abnormalities, poor growth, joint stiffness, and a prominent forehead. Hurler Syndrome is characterized by high concentrations of mucopolysaccharides, dermatan and heparan sulfates, in the urine. It is the most severe form. Symptoms first become evident at 6 months to 2 years of age with developmental delay, recurrent urine and upper respiratory infections, noisy breathing and a persistent nasal discharge. Hydrocephalus is commonly present after the age of 2-3 years. (For more information on this disorder, choose "hydrocephalus" as your search term in the Rare Disease Database.) Other physical manifestations of this disorder may include clouding of the cornea of the eye, unusually large tongue, misaligned teeth, the development of a curved back and severe joint stiffness with clawlike hands. Mental development of Hurler syndrome usually reaches a peak at about 2 years of age with progressive mental retardation thereafter. The milder form of Hurler Syndrome is known as Scheie syndrome. These patients have normal intelligence, stature and life expectancy, but suffer from physical symptoms such as stiff joints, clouding of the cornea, and flow of blood from the aorta back into the left ventricle of the heart (aortic regurgitation). The onset of symptoms in patients with Scheie syndrome usually occurs after the age of 5 years. However, diagnosis is commonly delayed to between 10 to 20 years of age. Hurler-Scheie syndrome is an intermediate form 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. Causes Hurler Syndrome in all three of its variations is transmitted genetically, with each parent contributing one recessive gene carrying exactly the same type of genetic inheritance. (Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, 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 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.) The enzyme that is normally present to break down the carbohydrates (mucopolysaccharides) that is missing in Hurler Syndrome I is alpha-L-iduronidase. Affected Population Hurler Syndrome tends to affect males and females equally with an incidence of about 1 in 100,000 live births. Related Disorders There are many types of Mucopolysaccharidoses. For more information on these diseases, choose "MPS Disorder" as your search term in the Rare Disease Database. DiFerrante Syndrome (mucopolysaccharidosis VIII) is a disorder described in a single patient 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 (mucopolysaccharidosis VIII) is not a valid medical disorder. The Mucolipidoses are a family of similar disorders, producing symptoms very much like those of the MPS disorders. For more information, choose "ML Disorder" for your search term in the Rare Disease Database. I-cell disease, or Mucolipidosis Type II, resembles Hurler syndrome and the two disorders are very difficult to distinguish. I-cell disease has similar physical and mental deterioration as MPS I, but usually occurs earlier and is more severe. I-cell disease is characterized by diffused deficiency of lysosomal enzymes within the cell and is not associated with excretion of mucopolysaccharides in the urine. (For more information on this disorder, choose I-cell as your search term in the Rare Disease Database.) Therapies: Standard Treatment of Hurler Syndrome is symptomatic and supportive. Physical therapy, medical and genetic counseling services will be useful to patient and family. Prenatal diagnosis is now possible for this disorder. Therapies: Investigational Since prenatal diagnosis is now possible through amniocentesis and sampling of a tissue layer in the embryo (chorionic villus sampling), new treatments aimed at checking early development of MPS including Hurler Syndrome are now under study. One method involves 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 genetic disorders such as MPS. Scientists are beginning to study fetal tissue transplants in children with Hurler Syndrome. Earlier studies in animals showed promising results with this form of trestmernt, but there is no way to predict that this will work in humans. The Mayo Clinic is investigating the use of Alpha Interferon as a treatment for Hurler Syndrome. For more information, physicians can contact: Morie A. Gertz, M.D. Dept. of Hematology & Internal Medicine Mayo Clinic Rochester, MN 55905 (507) 284-2511 This disease entry is based upon medical information available through November 1991. 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 Hurler Syndrome, 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 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 Society of Mucopolysaccharide Diseases, Inc. 382 Parkway Blvd. Flin Flon, Manitoba, Canada R8A OK4 Society of MPS Diseases 30 Westwood Drive Little Chalfont, Bucks, England For information on genetics and genetic counseling referrals, please contact: 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 MPS Society Brochure. MPS Research Funding Center Bulletin. BIRTH DEFECTS COMPENDIUM, 2nd ed.: Daniel Bergsma; March of Dimes, 1979. Pp. 727-729.