$Unique_ID{BRK04045} $Pretitle{} $Title{Neuropathy, Giant Axonal} $Subject{Neuropathy Giant Axonal GAN Giant Axonal Neuropathy Axonal Neuropathy Giant Congenital Giant Axonal Neuropathy Giant Axonal Disease Childhood Giant Axonal Neuropathy Seitelberger Disease Incontinentia Pigmenti } $Volume{} $Log{} Copyright (C) 1990 National Organization for Rare Disorders, Inc. 802: Neuropathy, Giant Axonal ** IMPORTANT ** It is possible that the main title of the article (Giant Axonal Neuropathy) is not the name you expected. Please check the SYNONYM listing to find the alternate names and disorder subdivisions covered by this article. Synonyms GAN Giant Axonal Neuropathy Axonal Neuropathy, Giant Congenital Giant Axonal Neuropathy Giant Axonal Disease Childhood Giant Axonal Neuropathy Information on the following disorders can be found in the Related Disorders section of this report: Seitelberger Disease Incontinentia Pigmenti 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. Giant Axonal Neuropathy is a genetic disorder that first appears during infancy. Major symptoms may include kinky hair, unusual leg posture, poor vision, impaired muscle coordination (ataxia) and weakness, and degenerative mental functioning (dementia). Symptoms Giant Axonal Neuropathy (GAN) may be characterized by symptoms such as loss of sensation in the legs and feet, impaired muscle coordination (ataxia) and weakness, decreased reflexes (hyporeflexia), and poor vision. Other senses such as hearing may also be affected. Mental retardation or seizures may occur. Tightly curled kinky hair, which may be extremely pale, is characteristic of GAN but is not present in all patients. Degenerative mental changes (dementia) may occur as the disorder progresses. Other symptoms may include unusual leg posture, involuntary rapid movements of the eyeball (nystagmus), wasting away of muscles possibly in all four limbs (amyotrophy), muscle twitches (fasciculations), and difficulty in articulation of speech (dysarthria). Giant Axonal Neuropathy is present at birth. Onset of the disorder occurs in infancy or very early childhood and it is slowly progressive. Both the central and peripheral nervous systems are involved. The central nervous system is comprised of the brain and spinal cord, while the peripheral nervous system spreads out from the brain and spinal cord to all other areas of the body. In Giant Axonal Neuropathy, a part of the nerve cell called the axon swells up with abnormal deposits of tiny threads of protein called "neurofilaments." Other filaments, called "intermediate filaments (IFS)", collapse into large clusters in a variety of cells such as nerves, muscles, and connective tissue cells and cells that produce colors (pigments). This causes degeneration and abnormal functioning especially affecting the peripheral nervous system. As the disorder progresses the central nervous system becomes involved. Occurring within the brain and spinal cord is the formation of fibrous deposits known as Rosenthal fibers. The corticospinal tract (the area around the spinal cord where nerve impulses direct the movement of muscles), cerebellum (the area of the brain concerned especially with muscle coordination and balance), and the white matter of the brain become affected. There is a progressive loss of axons within nerve cells as the disorder progresses. Diagnosis can be made by sural nerve biopsy. Causes Giant Axonal Neuropathy is a genetic disorder with an autosomal recessive inheritance. 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 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 Giant Axonal Neuropathy is a rare disorder present at birth. It affects males and females in equal numbers. Onset of the disorder occurs in infancy or very early childhood. Related Disorders Symptoms of the following disorders can be similar to those of Giant Axonal Neuropathy. Comparisons may be useful for a differential diagnosis: Seitelberger Disease is an inherited central nervous system disorder usually beginning before the age of two years. Children with Seitelberger Disease may experience difficulty in walking and/or speaking. A decreased sensitivity to pain may develop in the legs and trunk. Coordination may become impaired, and decreased muscle tone ("floppiness"), muscle spasms (spasticity) and/or weakening of reflexes may also occur. In later stages, involuntary rapid eye movements, progressive vision problems and seizures can occur. (For more information on this disorder, choose "Seitelberger Disease" as your search term in the Rare Disease Database). Incontinentia Pigmenti is a genetic dermatological disorder characterized by unusual patterns of discolored skin. These discolorations tend to improve with age. Abnormal deposits of normal skin pigment (melanin) cause these discolorations. Other oral, visual and/or neurological symptoms may also occur. Extremely kinky or wooly hair (Wooly hair nevus) and an immune system dysfunction have also been reported in a small number of patients with IP. (For more information on this disorder, choose "Incontinentia Pigmenti" as your search term in the Rare Disease Database). Therapies: Standard Treatment of Giant Axonal Neuropathy is symptomatic and supportive. Genetic counseling will be of benefit for patients and their families. Services for visually and/or mobility impaired people may be of assistance to people with Giant Axonal Neuropathy. Therapies: Investigational This disease entry is based upon medical information available through August 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 Giant Axonal Neuropathy, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Children's Brain Diseases Foundation for Research 350 Parnassus, Suite 900 San Francisco, CA 94117 (415) 566-5402 (415) 565-6259 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 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 MENDELIAN INHERITANCE IN MAN, 8th Ed.: Victor A. McKusick; Johns Hopkins University Press, 1986. Pp. 1107. CHILDHOOD GIANT AXONAL NEUROPATHY. CASE REPORT AND REVIEW OF THE LITERATURE. R. Tandan, et al.; J Neurol Sci (Dec 1987; issue 82 (1-3)). Pp. 205-228. CONGENITAL GIANT AXONAL NEUROPATHY. R.B. Kinney, et al,; Arch Pathol Lab Med (Jul 1985; issue 109 (7)). Pp. 639-641. GIANT AXONAL NEUROPATHY: A CONDITIONAL MUTATION AFFECTING CYTOSKELETAL ORGANIZATION. M.W. Klymkowsky, et al.; J Cell Biol (Jan 1985; issue 100 (1)). Pp. 245-250. GIANT AXONAL NEUROPATHY. A REVIEW. R.A. Ouvrier; Brain Dev (1989; issue 11 (4)). Pp. 207-214. GIANT AXONAL NEUROPATHY: CENTRAL ABNORMALITIES DEMONSTRATED BY EVOKED POTENTIALS. A. Majnemer, et al.; Ann Neurol (Apr 1986; issue 19 (4)). Pp. 394-396. GIANT AXONAL NEUROPATHY: CORRELATION OF CLINICAL FINDINGS WITH POSTMORTEM NEUROPATHOLOGY. C. Thomas, et al.; Ann Neurol (Jul 1987; issue 22 (1)). Pp. 79-84. GIANT AXONAL NEUROPATHY: OBSERVATIONS ON A FURTHER PATIENT. M. Donaghy, et al.; J Neurol Neurosurg Psychiatry (Jul 1988; issue 51 (7)). Pp. 991- 994. GIANT AXONAL NEUROPATHY WITH INHERITED MULTISYSTEM DEGENERATION IN A TUNISIAN KINDRED. M. Ben Hamida, et al.; Neurology (Feb 1990; issue 40 (2)). Pp. 245-250.