Ataxia with Vitamin E Deficiency

Ataxia with Vitamin E Deficiency

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Ataxia with Vitamin E Deficiency is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • AVED
  • Isolated Vitamin E Deficiency
  • Familial Isolated Vitamin E Deficiency

Disorder Subdivisions

  • None

General Discussion

Ataxia with vitamin E deficiency (AVED) is a rare inherited neurodegenerative disorder characterized by impaired ability to coordinate voluntary movements (ataxia) and disease of the peripheral nervous system (peripheral neuropathy). AVED is a progressive disorder that can affect many different systems of the body (multisystem disorder). Specific symptoms vary from case to case. In addition to neurological symptoms, affected individuals may experience eye abnormalities, disorders affecting the heart muscles (cardiomyopathy), and abnormal curvature of the spine (scoliosis). AVED is extremely similar to a more common disorder known as Friedreich's ataxia. AVED is inherited as an autosomal recessive trait.



Vitamin E deficiency often occurs secondary to disorders that impair the absorption of vitamin E from fat including liver disorders, disorders of fat metabolism, and disorders of bile secretion. These disorders include cholestasis (a syndrome of various causes characterized by impaired bile secretion); cystic fibrosis (primarily a lung disorder that may also affect bile secretion); primary biliary cirrhosis (a liver disorder that results in cholestasis); and abetalipoproteinemia (a digestive disorder characterized by fat malabsorption). Premature infants may have a low vitamin E reserve because only small amounts of vitamin E cross the placenta, and therefore they may become deficient if fed a formula high in unsaturated fats and low in vitamin E. In rare cases, vitamin E deficiency may be caused by a poor diet. (For more information on the above disorders, choose the specific disorder name your search term in the Rare Disease Database.)

Symptoms

AVED affects the central nervous system resulting in peripheral neuropathy and ataxia. Peripheral neuropathy is a general term that denotes a disorder of the peripheral nervous system. The peripheral nervous system consists of all the motor and sensory nerves that connect the brain and spinal cord to the rest of the body (i.e., the nerves outside the central nervous system). Individuals with AVED develop progressive weakness of the legs, which may appear as a staggering, lurching way of walking (gait) or trembling when an affected individual is standing still. Ataxia is defined as a failure of muscle coordination that generally results in an unsteady gait. Without treatment, AVED may progress to cause significant difficulties walking and, potentially over the course of many years, can result in an affected individual becoming wheelchair bound.



Additional neurological findings include partial loss of the sense of touch or sensitivity to pain and temperature may also occur. With time, reflexes in the legs may slow or be absent (areflexia), and an abnormally high-arched foot (pes cavus) may develop with overextension (hyperextension) of the big toe. Involvement of the throat muscles may lead to impaired swallowing and choking and may cause difficulty in eating. Slurred speech (dysarthria) may also be present. Some affected individuals may develop a tremor or shaking of the head (titubation). Intellect and emotions are rarely affected.



In addition to neurological symptoms, individuals with AVED may develop symptoms affecting other systems of the body including eye abnormalities such as retinitis pigmentosa (RP), which is one name for a large group of vision disorders that cause progressive degeneration of the membrane lining the eyes (retina) resulting in visual impairment. Some affected individuals may have yellow "fatty" deposits (xanthelasmata) in the retina.



Affected individuals may also develop lateral or sideways curvature of the spine (scoliosis), degenerative changes of the heart muscle (cardiomyopathy), or "fatty" deposits (xanthomas) affecting the Achilles tendon. Some individuals with AVED may experience a form of dystonia. Dystonia is the name for a group of movement disorders that is generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures).

Causes

AVED is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes; one received from the father and one from the mother.



Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual 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 for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.



Researchers have determined that AVED results from mutations of a gene on the long arm (q) of chromosome 8 (8q13.1-q13.3). The gene regulates production of a protein (alpha-tocopherol transfer protein) that binds vitamin E into fatty proteins (very-low-density lipoprotein or VLDL) produced and secreted by the liver. Individuals with AVED have an impaired ability to bind vitamin E into VLDL, which results in vitamin E deficiency in certain tissues.



The symptoms of AVED occur because of a deficiency of vitamin E, a fat-soluble vitamin that the body needs in very small amounts. It is stored in the body's fat. Therefore, it is not necessary to consume vitamin E daily, as long as adequate amounts are stored in the body from a well balanced diet. Vitamin E is found in various foods including vegetable oils, wheat germ, whole-grain cereals, egg yolk, and liver. The liver stores the vitamin E-containing fat. Bile breaks down dietary fat in the small intestine so that vitamins can be absorbed. Vitamin E is an antioxidant, a substance used by the body to protect cells from free radicals, which are atoms that are normal by-products of metabolism. Free radicals damage the cells of the body.

Affected Populations

AVED affects males and females in equal numbers. The disorder is estimated to occur in fewer than 1 in 1 million people. In Tunisia, the disorder is estimated to occur in 1 in 100,000 people. The onset of AVED may occur during childhood or adulthood with cases reported in children as young as two and adults as old as 52. The disorder was first described in the medical literature in 1981.

Standard Therapies

Diagnosis

A diagnosis of AVED is made based upon a thorough clinical evaluation, a detailed patient history and a variety of tests and characteristic findings (e.g. low levels of vitamin E with normal levels of lipoproteins and lipids and no evidence of fat malabsorption).



Treatment

Individuals with AVED are treated with vitamin E supplementation. Vitamin E treatment has often halted the progression of the disorder and, in some cases, improved existing neurological symptoms.



Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

TEXTBOOKS

Scott RM. Moyamoya Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:559.



Scriver CR, et al., eds. The Metabolic and Molecular Basis of Inherited Disease. 7th Ed. New York, NY; McGraw-Hill Companies, Inc; 1995:5845-55.



Menkes JH., au., Pine JW, et al., eds. Textbook of Child Neurology, 5th ed. Baltimore, MD: Williams & Wilkins; 1995:890-1.



Adams, RD, et al., eds. Principles of Neurology. 6th ed. New York, NY: McGraw-Hill, Companies; 1997:1155-6.



Lyon G, et al., eds. Neurology of Hereditary Metabolic Diseases in Childhood. 2nd ed. New York, NY: McGraw-Hill Companies; 1996:192.



JOURNAL ARTICLES

Min KC, et al. Crystal structure of human alpha-tocopherol transfer protein bound to its lingand: implications for ataxia with vitamin E deficiency. Proc Natl Acad Sci USA. 2003;100:14713-8.



Koenig M. Rare forms of autosomal recessive neurodegenerative ataxia. Semin Pediatr Neurol. 2003;10:183-92.



Roubertie A, et al. Ataxia with vitamin E deficiency and severe dystonia: report of a case. Brain Dev. 2003;25:442-5.



Angelini L, et al. Myoclonic dystonia as unique presentation of isolated vitamin E deficiency in a young patient. Mov Disord. 2002;17:612-4.



Benomar A, et al. Clinical comparison between AVED patients with 744 del A mutation and Friedreich ataxia with GAA expansion in 15 Moroccan families. J Neurol Sci. 2002;198:25-9.



Feki M, et al. Vitamin E deficiency. Etiopathogenesis, clinical, histopathologic, and electrical features, and main etiologies. Ann Med Interne. 2001;152:392-7.



Gabsi S, et al. Effect of vitamin E supplementation in patients with ataxia with vitamin E deficiency. Eur J Neurol. 2001;8:477-81.



Gosalakkal JA. Ataxias of childhood. Neurolog. 2001;7:300-6.



Alex G, et al. Ataxia with isolated vitamin E deficiency: a clinical, biochemical and genetic diagnosis. J Paediatr Child Health. 2000;36:515-6.



Martinello F, et al. Supplemental therapy in isolated vitamin E deficiency improves the peripheral neuropathy and prevents the progression of ataxia. J Neurol Sci. 1998;156:177-9.



Cavalier L, et al. Ataxia with isolated vitamin E deficiency: heterogeneity of mutations and phenotypic variability in a large number of families. Am J Hum Genet. 1998;62:301-10.



Yokota T, et al. Friedreich-like ataxia with retinitis pigmentosa caused by the His101Gln mutation of the alpha-tocopherol transfer protein gene. Ann Neurol. 1997;41:826-32. Comment in: Ann Neurol. 1998;43:273.



Ben Hamida M, et al. Friedreich's ataxia phenotype not linked to chromosome 9 and associated with selective autosomal recessive vitamin E deficiency in two inbred Tunisian families. Neurology. 1993;43:2179-83. Comment in: Neurology. 1993;43:2167-9.



Ben Hamida C, et al. Localization of Friedreich ataxia phenotype with selective vitamin E deficiency to chromosome 8q by homozygosity mapping. Nat Genet. 1993;5:195-200.



Trager MG, et al. Impaired ability of patients with familial isolated vitamin E deficiency to incorporate alpha-tocopheral into lipoproteins secreted by the liver. J Clin Invest. 1990;85:397-407.



Burck U, et al. Neuropathy and vitamin E deficiency in man. Neuropediatrics. 1981;12:267-78.



FROM THE INTERNET

McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:277460; Last Update:2/24/2003.

Available at: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=27746

Resources

March of Dimes Birth Defects Foundation

1275 Mamaroneck Avenue

White Plains, NY 10605

Tel: (914)997-4488

Fax: (914)997-4763

Tel: (888)663-4637

Email: Askus@marchofdimes.com

Internet: http://www.marchofdimes.com



National Ataxia Foundation

2600 Fernbrook Lane Suite 119

Minneapolis, MN 55447

USA

Tel: (763)553-0020

Fax: (763)553-0167

Email: naf@ataxia.org

Internet: http://www.ataxia.org



Retinitis Pigmentosa International

P.O. Box 900

Woodland Hills, CA 91365

Tel: (818)992-0500

Fax: (818)992-3265

Tel: (800)344-4877

Email: info@rpinternational.org

Internet: http://www.rpinternational.org



National Scoliosis Foundation

5 Cabot Place

Stoughton, MA 02072

Tel: (781)341-8333

Fax: (781)341-8333

Tel: (800)673-6922

Email: nsf@scoliosis.org

Internet: http://www.scoliosis.org



NIH/National Institute of Neurological Disorders and Stroke

P.O. Box 5801

Bethesda, MD 20824

Tel: (301)496-5751

Fax: (301)402-2186

Tel: (800)352-9424

TDD: (301)468-5981

Internet: http://www.ninds.nih.gov/



euro-ATAXIA

Lincoln House

Kennington Park

1-3 Brixton Road

London, SW9 6DE

United Kingdom

Tel: 4402075821444

Email: marco.meinders@euro-ataxia.eu

Internet: http://www.euro-ataxia.eu/



Canadian Association for Familial Ataxias - Claude St-Jean Foundation

3800 Radisson Street Office 110

Montreal

Quebec, H1M 1X6

Canada

Tel: 5143218684

Tel: 8553218684

Email: ataxie@lacaf.org

Internet: http://www.lacaf.org



Friedreich's Ataxia Research Alliance

533 W. Uwchlan Ave.

Downingtown, VA 19335

USA

Tel: (484)879-6160

Fax: (484)872-1402

Email: info@cureFA.org

Internet: http://www.curefa.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use . How this information was developed to help you make better health decisions.

Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.