$Unique_ID{BRK03440} $Pretitle{} $Title{Alexander's Disease} $Subject{Alexander's Disease Leukodystrophy with Rosenthal Fibers Megalencephaly with Hyaline Inclusion Fibrinoid Degeneration of Astrocytes Megalencephaly with Hyaline Panneuropathy Fibrinoid Leukodystrophy Hyaline Panneuropathy Dysmyelogenic Leukodystrophy Dysmyelogenic Leukodystrophy-Megalobarencephaly Hydrocephalus Multiple Sclerosis Astrocytoma, Malignant Astrocytoma, Benign Adrenoleukodystrophy Canavan's Leukodystrophy Metachromatic Leukodystrophy Pelizaeus-Merzbacher Brain Sclerosis National} $Volume{} $Log{} Copyright (C) 1986, 1987, 1988, 1990, 1993 National Organization for Rare Disorders, Inc. 56: Alexander's Disease ** IMPORTANT ** It is possible that the main title of the article (Alexander's Disease) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Leukodystrophy with Rosenthal Fibers Megalencephaly with Hyaline Inclusion Fibrinoid Degeneration of Astrocytes Megalencephaly with Hyaline Panneuropathy Fibrinoid Leukodystrophy Hyaline Panneuropathy Dysmyelogenic Leukodystrophy Dysmyelogenic Leukodystrophy-Megalobarencephaly Information on the following diseases can be found in the Related Disorders section of this report: Hydrocephalus Multiple Sclerosis Astrocytoma, Malignant Astrocytoma, Benign Adrenoleukodystrophy Canavan's Leukodystrophy Metachromatic Leukodystrophy Pelizaeus-Merzbacher Brain Sclerosis 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. Alexander's Disease is an extremely rare, progressive, metabolic, neurological disorder that is frequently inherited. It is one of a group of diseases known as the leukodystrophies. Alexander's Disease is characterized by loss of the fatty layers that cover nerves (demyelination), and the formation of abnormal bodies (Rosenthal fibers) in supporting cells (astrocytes) of the brain. These Rosenthal fibers most frequently form on the surface of the brain and around the blood vessels within the brain. The symptoms of Alexander's Disease usually begin during infancy and are associated with mental and physical retardation. Juvenile (occuring later than infancy) and adult-onset Alexander's Disease are recognized forms of this disorder but occur very infrequently. Symptoms The early symptoms of Alexander's Disease that occur during infancy include muscle spasms and mental as well as physical retardation. Infants with this disorder typically have an abnormally large head (megalencephaly), and failure to thrive. When symptoms begin in childhood rather than infancy, the child experiences a progressive loss of previously acquired motor and mental skills. As this disease progresses, seizures may occur. Juvenile-onset Alexander's Disease begins during childhood or adolescence and generally has a long course. Symptoms are similar to the infantile form of this disorder but may also include difficulty swallowing, painful joints, vomiting, respiratory difficulties, the inability to cough, and/or muscle spasms. Alexander's Disease may also begin during adulthood. There may be few or no symptoms but abnormal bodies (Rosenthal fibers) in the supporting cells (astrocytes) appear in the brain. Computer tomography (CT scan) and magnetic resonance imaging (MRI) can confirm the presence of Rosenthal fibers and the diagnosis of this very rare form of leukodystrophy. Rosenthal fibers are not exclusively found in Alexander's Disease, but sometimes occur in other neurological conditions. If an adult does have symptoms of Alexander's Disease, they are frequently confused with those of Multiple Sclerosis or the growth of Benign or Malignant Astrocytes. (For information on these diseases, see the related disorders section of this report.) These symptoms may include headaches, numbness or tingling in the arms and legs, difficulty walking, visual impairment, muscle weakness, fatigue, and/or intellectual impairment. Causes The exact cause of Alexander's Disease is not known and the metabolic defect that causes this disease has not yet been identified. It is thought that Alexander's Disease may be inherited as an autosomal recessive genetic trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, 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 for the same trait 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 not show 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 Alexander's Disease is an extremely rare disorder that affects males and females in equal numbers. Related Disorders Symptoms of the following disorders can be similar to those of Alexander's Disease. Comparisons may be useful for a differential diagnosis: Hydrocephalus is a condition in which the normal flow of cerebrospinal fluid (CSF) is restricted and the spaces in the brain (ventricles) become abnormally enlarged. Fluid accumulates beneath the skull and puts pressure on the brain. Hydrocephalus is characterized in children by an abnormally enlarged head (megalencephaly). The scalp may be thin and transparent, and the forehead may bulge (frontal bossing). Other symptoms of Hydrocephalus may include convulsions, abnormal reflexes, a slowed heartbeat, headache, vomiting, weakness and/or problems with vision. (For more information on this disorder, choose "Hydrocephalus" as your search term in the Rare Disease Database.) Multiple Sclerosis is a chronic disorder of the central nervous system (CNS) that causes the destruction of the fatty covering on nerves (demyelination). The symptoms of this disease vary greatly and may include visual impairment, double vision and/or involuntary rhythmic movements of the eyes (nystagmus), impairment of speech, numbness or tingling sensations in the arms and legs, muscle weakness and/or difficulty walking. The symptoms of Multiple Sclerosis may be similar to those of Adult-Onset Alexander's Disease. (For more information on this disorder, choose "Multiple Sclerosis" as your search term in the Rare Disease Database.) Astrocytomas are brain tumors that can be either benign or malignant and are composed of large, star shaped cells (astrocytes). Symptoms may vary according to the size, location, and growth rate of the tumor. Frequently the first symptom is a recurrent headache that is typically a result of increased pressure within the skull due to the growth of the tumor. Headaches may be accompanied by vomiting and/or personality changes. Other symptoms of Benign or Malignant Astrocytomas may include irritability, emotional instability, memory loss, intellectual impairment, convulsions, paralysis, and/or seizures. (For more information on this disorder, choose "Astrocytoma" as your search term in the Rare Disease Database.) Adrenoleukodystrophy is a form of Leukodystrophy. It is a rare inherited metabolic disorder characterized by the accumulation of very long chain fatty acids (VLCFA) in the brain that causes the progressive loss of the fatty covering (myelin sheath) on nerves within the brain. This disorder also causes progressive degeneration of the adrenal gland (adrenal atrophy). Symptoms of the childhood form of Adrenoleukodystrophy, which affects only males, may include loss of previously acquired intellectual skills, poor memory, loss of emotional control, a jerky uncoordinated walk (ataxia), and/or muscle weakness on one side of the body. Other symptoms may include difficulties with speech, hearing loss, and/or visual impairment. (For more information on this disorder, choose "Adrenoleukodystrophy" as your search term in the Rare Disease Database.) Canavan's Leukodystrophy is another rare, inherited form of leukodystrophy characterized by the progressive deterioration of the central nervous system. Symptoms of this disorder may include floppiness, the loss of previously acquired mental and motor skills, poor head control, an abnormally enlarged head (megalencephaly) and/or blindness. As Canavan's Leukodystrophy progresses, there may be spastic muscle contractions in the arms and legs and paralysis. This disorder is caused by a chemical imbalance in the brain and symptoms typically appear in early infancy. (For more information on this disorder, choose "Canavan's Leukodystrophy" as your search term in the Rare Disease Database.) Metachromatic Leukodystrophy is a rare inherited leukodystrophy characterized by the abnormal accumulation of a fatty-like substance (sphingolipid) in the brain and other tissues of the body. Symptoms of this disorder may include muscle rigidity, visual impairment, and/or convulsions. Previously acquired physical and intellectual skills may be lost. This disorder may begin in infancy, adolescence, or adulthood. (For more information on this disorder, choose "Metachromatic Leukodystrophy" as your search term in the Rare Disease Database.) Pelizaeus-Merzbacher Brain Sclerosis is a very rare inherited leukodystrophy characterized by the degeneration of the brain caused by the loss of fatty myelin sheath covering the nerves (demyelination). This disorder may begin in infancy or adulthood. The first symptoms in an infant include failure to thrive, developmental delays, muscle spasms, unsteadiness, weakness, and/or visual impairment. Deformities of the bones and convulsions are sometimes seen. (For more information on this disorder, choose "Pelizaeus-Merzbacher" as your search term in the Rare Disease Database.) Therapies: Standard The treatment of Alexander's Disease is symptomatic and supportive. Genetic counseling may be of benefit for patients and their families. Therapies: Investigational Current research on Alexander's Disease is focused on identifying the exact composition of the Rosenthal fibers and the factors responsible for their formation and growth. Recent progress has been made in identifying at least two compounds that are present in Rosenthal fibers. These findings may eventually lead to new methods of diagnosis and in time may lead to the development of new treatments for Alexander's Disease. Research on birth defects and their causes is ongoing. The National Institutes of Health (NIH) is sponsoring the Human Genome Project that is aimed at mapping every gene in the human body and learning why they sometimes malfunction. It is hoped that this new knowledge will lead to prevention and treatment of genetic disorders in the future. This disease entry is based upon medical information available through April 1993. 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 Alexander's Disease, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 United Leukodystrophy Foundation 2304 Highland Drive Sycamore, IL 60178 (815) 895-3211 (800) 728-5483 Children's Brain Diseases Foundation 350 Parnassus, Suite 900 San Francisco, CA 94117 (415) 566-4402 (415) 565-6259 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 Genetic Information and Genetic Counseling Referrals: 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 METABOLIC BASIS OF INHERITED DISEASE, 6th Ed.: Charles R. Scriver, et al., eds.; McGraw Hill, 1989. Pp. 1699-1705. MENDELIAN INHERITANCE IN MAN, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 1207-1208. BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief; Blackwell Scientific Publications, 1990. Pp. 83-84. PRINCIPLES OF NEUROLOGY, 4th Ed.; Raymond D. Adams, M.D. and Maurice Victor, M.D., Editors; McGraw-Hill Information Services Company, 1989. Pp. 789-791, 970-971. PROGRESSIVE FIBRINOID DEGENERATION OF FIBRILLARY ASTROCYTES ASSOCIATED WITH MENTAL RETARDATION IN A HYDROCEPHALIC INFANT: W.S. Alexander: Brain (Issue 1949:72). Pp. 373-381. ALEXANDER'S DISEASE. D. Borrett. Brain (Jun 1985; 108(Pt 2)). Pp. 367- 385.