$Unique_ID{BRK03938} $Pretitle{} $Title{Leukodystrophy, Metachromatic} $Subject{Leukodystrophy, Metachromatic MLD Arylsulfatase A Deficiency ARSA Metachromatic Form of Diffuse Cerebral Sclerosis Diffuse Cerebral Sclerosis Cerebroside Sulfatase Deficiency Greenfield Disease Leukoencephalopathy Metachromatic Leukoencephalopathy Sulfatide Lipidosis Sulfatidosis Late Infantile Metachromatic Leukodystrophy Juvenile MLD Juvenile Onset Metachromatic Leukodystrophy Adult Metachromatic Leukodystrophy Metachromatic Leukodystrophy Cerebroside Sulfatase Activator} $Volume{} $Log{} Copyright (C) 1986, 1987, 1988 National Organization for Rare Disorders, Inc. 212: Leukodystrophy, Metachromatic ** IMPORTANT ** It is possible the main title of the article (Metachromatic Leukodystrophy) is not the name you expected. Please check the SYNONYMS listing to find the alternate names and disorder subdivisions covered by this article. Synonyms MLD Arylsulfatase A Deficiency ARSA Metachromatic Form of Diffuse Cerebral Sclerosis Diffuse Cerebral Sclerosis Cerebroside Sulfatase Deficiency Greenfield Disease Leukoencephalopathy Metachromatic Leukoencephalopathy Sulfatide Lipidosis Sulfatidosis DISORDER SUBDIVISIONS Late Infantile Metachromatic Leukodystrophy Juvenile MLD, also known as Juvenile Onset Metachromatic Leukodystrophy Adult Metachromatic Leukodystrophy Metachromatic Leukodystrophy Due to Lack of Cerebroside Sulfatase Activator 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. Metachromatic Leukodystrophy (MLD) is an autosomal recessive inherited disease which affects the brain and spinal cord. The disease is characterized by progressive paralysis and dementia. It appears in the following forms: (Late) Infantile Metachromatic Leukodystrophy Onset of this form of the disorder is usually in the second year of life. Clinical features are motor impairment, rigidity, mental deterioration and sometimes convulsions. Juvenile Metachromatic Leukodystrophy Onset of Juvenile MLD occurs between the ages of 4 and 10 years. Adult Metachromatic Leukodystrophy Onset of this form of MLD occurs after 16 years of age. Dystonia (abnormal muscle tone) and impaired articulation or stuttering (dysarthria) is a symptom of Adult MLD. Metachromatic Leukodystrophy Due to Deficiency of Cerebroside Sulfatase Activator The clinical picture for this type of Leukodystrophy is the same as Juvenile MLD. Symptoms The manifestations of Metachromatic Leukodystrophy (MLD) usually begin gradually in a child or adult who previously has appeared healthy. Most commonly, some subtle change in the patient's thought processes, memory, behavior, or gait will be noticeable. Sometimes a disturbance in vision, or less commonly in hearing, or numbness in parts of the body may be the first symptom. Often in the early stages of the disorder, the signs and symptoms of Metachromatic Leukodystrophy are vague and difficult to recognize or diagnose. Causes Metachromatic Leukodystrophy (MLD) is an autosomal recessive inherited disorder caused by a deficiency in the enzyme arylsulfatase A. Arylsulfatase A is an enzyme which acts on the sulfatide of the fatty white sheath (myelin) of the nerve cells in the brain and the spinal cord. (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 Metachromatic Leukodystrophy affects persons of both sexes and all nationalities. Related Disorders Amaurotic Familial Idiocy (Tay-Sachs disease) is a genetic Disorder occurring in children which causes progressive deterioration of the central nervous system. It is generally found among children with Jewish heritage and becomes clinically evident at about 6 months of age. Sandhoff Disease, a variant of Tay-Sachs Disease, is clinically indistinguishable from the more common form of Tay-Sachs Disease, but occurs in the general population. (For more information on the above disorders, choose "Tay-Sachs" and "Sandhoff" as your search term in the Rare Disease Database.) Therapies: Standard Treatment of Metachromatic Leukodystrophy is symptomatic and supportive. Therapies: Investigational Current research is directed toward the identification and cloning of genes, and defining the specific gene abnormality responsible for the leukodystrophy. Bone marrow transplantation is being researched as a possible treatment for Metachromatic Leukodystrophy patients. This involves extracting cross-matched bone marrow from a healthy donor and injecting it into the patient. The healthy bone marrow cells enter the general circulation and migrate through the blood to marrow cavities in the patient's bones. The new marrow cells begin to grow and produce new white blood cells and platelets. This procedure involves risks which must be balanced against possible benefits. It is used experimentally in the most severe cases of this disorder. Bone marrow transplantation is being tested as a treatment for late infantile Metachromatic Leukodystrophy. Bone marrow transplantation is not recommended for patients with relatively advanced neurological symptoms. More research is needed to determine the safety and effectiveness of this procedure. This disease entry is based upon medical information available through April 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 Metachromatic Leukodystrophy, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 United Leukodystrophy Foundation, Inc. 2304 Highland Drive Sycamore, IL 60178 (815) 895-3211 (800) 728-5483 National Tay-Sachs and Allied Diseases Association, Inc. 2001 Beacon St, Rm. 304 Brookline, MA 02164 (617) 277-4463 or 277-3965 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 Association Europeenne contre les Leucodystrophies 7 Rue Pasteur 54000 NANCY France 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 THE MERCK MANUAL 15th ed: R. Berkow, et al: eds; Merck, Sharp & Dohme Research Laboratories, 1987. P. 1013. CECIL TEXTBOOK OF MEDICINE, 18th ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Eds.: W. B. Saunders Co., 1988. P. 2215-6.