$Unique_ID{BRK03965} $Pretitle{} $Title{Mannosidosis} $Subject{Mannosidosis Lysosomal Alpha-D-Mannosidase Deficiency Mucopolysaccharidosis, Type I Pseudo-Hurler Polydystrophy } $Volume{} $Log{} Copyright (C) 1987, 1988, 1990 National Organization for Rare Disorders, Inc. 420: Mannosidosis ** IMPORTANT ** It is possible the main title of the article (Mannosidosis) is not the name you expected. Please check the SYNONYMS listing on the next page to find alternate names, disorder subdivisions, and related disorders covered by this article. Synonyms Lysosomal Alpha-D-Mannosidase Deficiency Information on the following diseases can be found in the Related Disorders section of this report: Mucopolysaccharidosis, Type I Pseudo-Hurler Polydystrophy 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. Mannosidosis is a genetic disorder characterized by a lysosomal enzyme deficiency resulting in progressive mental and physical deterioration. A deficiency of the enzyme alpha-D-mannosidase causes the symptoms of this disorder which can vary in severity. Symptoms of the most severe form may begin within the first year of life while a milder form may begin during juvenile or adult years. Symptoms Symptoms of the most severe form of Mannosidosis may begin within the first year of life. This form is characterized by rapid progression of mental retardation, liver and spleen enlargement, skeletal abnormalities, and coarse facial features. A milder form of this disorder involves normal early development although mild to moderate mental retardation may develop during childhood or adolescence. The clinical progression of the disease appears to slow down or stop beyond school age in some patients. Facial abnormalities such as a prominent forehead and jaw, a flattened nose, widely spaced or unevenly developed teeth, a thick tongue and lips, and clouded eye lenses or corneas may develop in both forms of Mannosidosis. The abdomen may become distended with enlargement of the liver and spleen. Growth rates can fluctuate with accelerated early growth, but subsequent impaired growth causing short stature. Thin arms and/or legs with stiff joints may develop. Spinal abnormalities may lead to extreme curvature in some cases. A diminished immune system response can make patients overly susceptible to bacterial infections, particularly of the respiratory system. Hearing loss may occur in either form of Mannosidosis. Causes Mannosidosis is inherited as an autosomal recessive trait. (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.) Symptoms are caused by an inborn error of enzyme metabolism involving abnormal accumulations of carbohydrate compounds (mannose-rich glycoproteins and oligosaccharides) in various tissues and body fluids. Affected Population Mannosidosis is a very rare disorder probably affecting only a few hundred people in the United States. This disorder affects males and females in equal numbers. Related Disorders Symptoms of the following disorders can be similar to Mannosidosis. Comparisons may be useful for a differential diagnosis: 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. A deficiency of the enzyme alpha-L-iduronidase causes symptoms of Type I MPS disorders. (For more information on MPS Disorders, choose "MPS" as your search term in the Rare Disease Database). Pseudo-Hurler Polydystrophy (Mucolipidosis III) is a genetic disorder beginning during childhood. This disorder is characterized by symptoms such as painless joint stiffness, decreased mobility, short stature, some coarseness of the facial features, mild mental retardation, multiple defective bone formations, and aortic valve heart disease. Mobility may gradually diminish until puberty after which no further changes occur. Pseudo-Hurler Polydystrophy is a milder form of I-cell Disease (Mucolipidosis II). (For more information on Pseudo-Hurler Polydystrophy, use "I-Cell" as your search term in the Rare Disease Database). Therapies: Standard Treatment of Mannosidosis is symptomatic and supportive. Genetic counseling may be of benefit for patients and their families. Therapies: Investigational Bone marrow transplants as a means of enzyme replacement is under investigation for treatment of lysosomal storage disorders, such as Mannosidosis. More research is needed before direct enzyme replacement therapy or bone marrow transplants can be recommended for use in treating patients with Mannosidosis. Pediatric hematologists are developing an international registry for Blackfan-Diamond Anemia. Families are urged to contact: Dr. Blanche P. Alter Mt. Sinai Medical Center Division of Hematology One Gustave Levy Place New York, NY 10029 (212) 241-8109 This disease entry is based upon medical information available through March 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 Mannosidosis, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 736-6518 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 Research Trust for Metabolic Diseases in Children Golden Gates Lodge, Weston Rd. Crewe CW1 1XN, England Telephone: (0270) 250244 For genetic information 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