$Unique_ID{BRK04205} $Pretitle{} $Title{Sanfilippo Syndrome} $Subject{Sanfilippo Syndrome Mucopolysaccharidosis Type III MPS III Oligophrenic Polydystrophy Polydystrophia Oligophrenia MPS Disorder Sanfilippo Type A Sanfilippo Type B} $Volume{} $Log{} Copyright (C) 1988, 1987, 1989, 1990 National Organization for Rare Disorders, Inc. 290: Sanfilippo Syndrome ** IMPORTANT ** It is possible the main title of the article (Sanfilippo 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 III MPS III Oligophrenic Polydystrophy Polydystrophia Oligophrenia MPS Disorder DISORDER SUBDIVISIONS Sanfilippo Type A Sanfilippo Type B 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. Sanfilippo Syndrome (MPS III), an autosomal recessive hereditary disorder, is characterized by severe mental deterioration, mild physical defects and the excretion of heparan sulfate in the urine. There are four types of Sanfilippo Syndrome; types A and B are the most common forms. Symptoms Patients with Sanfilippo Syndrome (MPS Type III) usually appear normal at birth, but mental retardation is usually evident by age 3-5 years. Mental and motor development reach a peak by 3-6 years of age after which behavioral disturbances and intellectual decline usually occur. Growth is usually minimally affected; the head may be enlarged, and abnormal hairiness (hirsutism) may occur. Mild coarsening of facial features, limitation of joint mobility and moderate enlargement of the liver and spleen (hepatosplenomegaly) also characterize this disorder. Deafness may also occur. The different forms of Sanfilippo Syndrome have identical clinical features, but can be distinguished by enzymatic assay. Sanfilippo A is characterized by a lack of heparan sulfate sulfatase; patients with Sanfilippo B lack N-acetyl-alpha-glucosaminidase. Heparan sulfate is the only mucopolysaccharide excreted in the urine. The deficient enzymes of the Sanfilippo subtypes are heparan N-sulfatase (type A), N- acethylglucosaminidase (type B), acetylcoA: gamma-glucosamine-N- acetyltransferase (type C), and N-acetyl-gamma-glucosamine-6-sulfatase (type D). Causes All types of Sanfilippo Syndrome are autosomal recessively inherited disorders. (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.) Affected Population Sanfilippo Syndrome may affect males and females equally. The disorder occurs in about 1 in 50,000 live births. Related Disorders There are many types of Mucopolysaccharidoses. (For more information, choose "MPS Disorder" as your search term in the Rare Disease Database.) Patients with MPS Type III are more similar to MPS Type II patients than those with other forms of Mucopolysaccharidoses. 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 is not a valid medical disorder. Therapies: Standard Treatment of Sanfilippo Syndrome is symptomatic and supportive. Genetic counseling may be helpful to the parents of patients with Sanfilippo Syndrome. 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 Sanfilippo 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 may someday be made available to people with genetic disorders such as Sanfilippo Syndrome. The Mayo Clinic is investigating the use of Alpha Interferon as a treatment for Sanfilippo 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 June 1990. 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 Sanfilippo 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 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 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 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. BIRTH DEFECTS COMPENDIUM, 2nd ed.: Daniel Bergsma, ed: March of Dimes, 1979. P. 731. MENDELIAN INHERITANCE IN MAN, 6th ed.: Victor A. McKusick; Johns Hopkins University Press, 1983. P. 839.