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Hereditary Ataxia


Hereditary Ataxia is a group of rare genetic neuromuscular disorders. It is characterized by degenerative changes in the brain and spinal cord. It can affect a person anytime between infancy through adulthood. Major symptoms include lack of coordination of the muscles used for voluntary movement.

1 Synonyms
2 Symptoms
3 Causes
4 Therapies: Standard
5 Therapies: Investigational
6 Resources
7 References

Synonyms
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Progressive Cerebellar Ataxia


Disorder Subdivisions:

Friedreich's Ataxia
Marie's Ataxia
Ataxia Telangiectasia
Vasomotor Ataxia
Vestibulocerebellar
Ataxiadynamia
Ataxiophemia
Olivopontocerebellar Atrophy
Charcot-Marie-Tooth Disease

Symptoms
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The Ataxia's are progressive neuromuscular disorders characterized by unsteadiness in walking or tremors of the arms and legs. Depending on which part of the brain is affected there may be muscle weakness and wasting which usually occurs when the lower motor neurons are affected. Some types of Ataxia may be complicated by vision disorders such as optic atrophy, retinitis pigmentosa, ophthalmaplegia (face and eye paralysis), nerve deafness or mental deterioration. There may also be skeletal changes such as scoliosis (bent spine) and deformities of the feet. Other medical problems may occur in relation to Ataxia such as heart disease, breathing problems, bone abnormalities and diabetes.

Disorder Subdivisions:

Olivopontocerebellar Atrophy is a group of inherited forms of Ataxia characterized by progressive neurological degeneration affecting the olivopontocerebellar area of the brain. These inherited forms include Menzel type I, Fickler-Winkler type II, retinal degeneration type III, Schut- Haymaker type IV, and ophthalmoplegia (paralysis of facial and eye muscles) type V OPCA.

Olivopontocerebellar Atrophy I (Menzel type OPCA) is inherited as a dominant trait and usually begins in the third or fourth decades of life, with an average onset at thirty years of age. In addition to cerebellar degeneration, other areas of the body become affected with speech abnormalities and/or tremors of the limbs. Involuntary movements (chorea) may also occur.

Olivopontocerebellar Atrophy II (OPCA II, Fickler-Winkler or deJerine- Thomas type) is inherited as a recessive trait and differs from OPCA type I by showing a lack of involuntary movements. Onset of this disorder usually begins at approximately fifty years of age. The exact nature of this form of cerebellar atrophy is not well understood.

Olivopontocerebellar Atrophy III (OPCA III; OPCA with retinal degeneration) is characterized by retinal degeneration. This form of OPCA usually begins during middle age, although it can begin at any age. It is also marked by blindness, tremor, weakness and impaired muscle coordination.

Olivopontocerebellar Atrophy IV (OPCA IV, Schut-Haymaker type OPCA) is inherited as a dominant trait and is characterized by a form of paralysis (spastic paraplegia). The atrophy seems to be limited to the inferior olivary nucleus and cerebellum with varying involvement of the pons area of the brain. Abnormalities of the spinal cord and some of the cranial nerves may also occur. Symptoms usually begin at approximately twenty-five years of age.

Olivopontocerebellar Atrophy V (OPCA V, OPCA with dementia and extrapyramidal signs) is characterized by cerebellar atrophy, tremors, ataxia, abnormal sensations, rigidity and mental deterioration. This disorder is inherited as a dominant trait and usually begins during adult life. Walking, writing and speech often become difficult as the disorder progresses.

Charcot-Marie-Tooth Disease (also known CMT Disease and Peroneal Muscular Atrophy) is usually inherited as a dominant trait. However, in some families it can occur as a recessive trait or even as an X-linked trait. This hereditary form of ataxia is characterized by weakness and atrophy, primarily in the legs. Disappearance of the fatty shield surrounding the nerves (segmental demyelination of peripheral nerves), and associated degeneration of part of the nerve cells (axons) characterize this disorder. When it is passed to offspring as an X-linked trait it affects only males.

Friedreich's Ataxia is a recessive type of hereditary neuromuscular syndrome characterized by slow degenerative changes of the spinal cord and the brain. Dysfunction of the central nervous system affects coordination of the muscles in the limbs. Speech can be affected and numbness or weakness of the arms and legs develop. Various transitional and overlapping forms of Friedreich's Ataxia can occur. Although no specific treatment can stop the progression of the disorder, some symptoms can be alleviated with proper treatment. In a few cases, spontaneous remissions may occur which can last five to ten years or sometimes longer. This syndrome appears to be the most common of the many forms of hereditary Ataxia. It usually begins during childhood or the teen years.

Marie's Ataxia is a neuromuscular syndrome inherited as a dominant trait. Also known as Pierre Marie's Disease or Hereditary Cerebellar Ataxia, it is characterized by a later onset of neurological and coordination disturbances. The syndrome usually begins between thirty and forty years of age and may not be as disabling as Friedreich's Ataxia. Initially, those affected may walk unsteadily and tend to fall frequently. Loss of coordination in the arms and speech disturbances may also occur. In later stages slight loss of vision, and loss of pain or touch sensations, may also occur. Tremors may develop when conscious motion is attempted. Swallowing and clearing of secretions may eventually become difficult if the throat muscles are affected.

Ataxia Telangiectasia, also known as Louis-Bar Syndrome, is inherited as a recessive trait. It is a progressive cerebellar ataxia that usually begins during infancy. It involves progressive loss of coordination in the limbs, head and eyes with a below-normal immune response to infections. In later stages, dilated blood vessels (telangiectasias) appear in the eyes and skin. Individuals with this form of Ataxia are more susceptible to sinus and lung infections and tend to have tumors (neoplasms). Ataxia Telangiectasia may be misdiagnosed as Friedreich Ataxia until dilated blood vessels appear in the skin (telangiectasias).

Vasomotor Ataxia is a dominant form of autonomic ataxia causing an unsteady walk and irregularity in the circulation marked by flushing and blanching of the skin due to spasms of the smaller blood vessels.

Vestibulocerebellar Ataxia is inherited as a dominant trait. It is due to disease of the central vestibular system or it's cerebellar components. Characterized by unsteady gait, incoordination of arm and leg movements and constant movement of the eyeballs (nystagmus).

Ataxiadynamia is a lack of coordination combined with muscular weakness. It is usually inherited as a dominant trait.

Ataxiophemia is inherited as a dominant trait. It is characterized by incoordination of the muscles concerned in speech production.

Causes
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Some forms of hereditary Ataxia are inherited as a dominant trait. In other forms it may be passed to offspring through recessive genes.

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 dominant disorders a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the other normal gene and resulting in appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is fifty percent for each pregnancy regardless of the sex of the resulting child.

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.

Some forms of Ataxia are not hereditary and can occur as a result of severe infections or side effects of drugs. In many cases Ataxia is a symptom of another neurological disorder rather than a distinct and separate illness.

Therapies: Standard
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Treatment of Ataxia is symptomatic and supportive. Continuous medical supervision to avoid potential complications involving the heart, lungs, spine, bones and muscles is recommended. Mental functions usually remain unaffected in most forms of hereditary ataxia but emotional strain can affect patients and their families. In such cases, psychological counseling may be helpful. Physical therapy may be helpful when recommended by a physician. Various aids may assist muscular movement. Drugs may be useful in treating some symptoms of Ataxia. Propanalol may be effective against static tremors, and less often against intention tremors. Dantrolene Sodium may help some patients with muscle spasms of the legs. Genetic counseling will be of benefit for patients and families affected by the hereditary ataxias.

Therapies: Investigational
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The multiprogrammable spinal cord stimulator involves epidural spinal electrostimulation (ESES). This is a medical device being tested for neuromuscular disorders. The device must be surgically implanted. The goal is to increase the range of mobility and alleviate muscle spasms and pain. A controlled study of ESES devices is being conducted by:

Neuromed
5000 Oakes Rd.
Ft. Lauderdale, FL 33314
(305) 584-3600

Clinical trials of the orphan drug physostigmine salicylate (Antilirium) for treatment of inherited forms of Ataxia are underway. For additional information physicians can contact:

Forrest Pharmaceuticals
2510 Metro Boulevard
Maryland Heights, MO 64043-99

This disease entry is based upon medical information available through June 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
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For more information on Hereditary Ataxia, please contact:

National Organization for Rare Disorders (NORD)
P.O. Box 8923
New Fairfield, CT 06812-1783
(203) 746-6518
(203) 746-6927 (TDD for the hearing impaired)

National Ataxia Foundation
2600 Fernbrook Lane, Site 119
Minniapolis, MN 55447-4752
Phone: (763) 553-0020
Email: naf@ataxia.org

NIH/National Institute of Neurological Disorders & Stroke (NINDS)
9000 Rockville Pike
Bethesda, MD 20892
(301) 496-5751
(800) 352-9424

International Tremor Foundation
833 W. Washington Blvd.
Chicago, IL 60607
(312) 733-1893

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
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MENDELIAN INHERITANCE IN MAN, 8th ed.: Victor A. McKusick; Johns Hopkins University Press, 1986. Pp. 84.

INTERNAL MEDICINE, 2nd Ed.: Jay H. Stein, ed.-in-chief; Little, Brown and Co., 1987. Pp.2160.

SPINOCEREBELLAR ATAXIA: LOCALIZATION OF AN AUTOSOMAL DOMINANT LOCUS BETWEEN TWO MARKER ON HUMAN CHROMOSOME 6; S.S. Rich, et al.; Am J Hum Genet, (October, 1987, issue 41 (4)). Pp. 524-531.

BRAIN CHOLINE ACETYLTRANSFERASE REDUCTION IN DOMINANTLY INHERITED OLIVOPONTOCEREBELLAR ATROPHY; J.J. Kish, et al.; Ann Neurol (August, 1987, issue 22 (2)). Pp. 272-275.