Years published: 1989, 1990, 2003, 2004, 2023
NORD gratefully acknowledges Samantha Irving, Master of Human Genetics and Genomic Data Analytics candidate from Keck Graduate Institute School of Pharmacy and Health Sciences and Rebecca Tran, PhD, Associate Professor of Clinical Sciences at Keck Graduate Institute School of Pharmacy and Health Sciences and the Department of Clinical and Administrative Sciences for assistance in the preparation of this report.
Ataxia with vitamin E deficiency (AVED) is a rare progressive neurodegenerative disorder affecting movement and motor control caused by very low vitamin E levels in the blood. Vitamin E is found in food sources and is necessary for proper health, as it acts as an important antioxidant that protects cells in the body from damaging molecules called free radicals. Individuals with AVED are unable to retain and use vitamin E from the diet. AVED can affect many different systems of the body such as the central nervous system (brain and spinal cord), eyes and heart. Without adequate levels of vitamin E, individuals with AVED have neurological issues like trouble coordinating movements (ataxia) and speech (dysarthria), loss of reflexes in the legs (lower limb areflexia) and a loss of sensation in the limbs (peripheral neuropathy). Additionally, an individual with AVED may experience eye abnormalities (retinitis pigmentosa), disorders affecting the heart muscles (cardiomyopathy) and abnormal curvature of the spine (scoliosis). AVED is very similar to Friedreich’s ataxia, which is a more common disorder. AVED is inherited in an autosomal recessive pattern and caused by a changes (mutations or pathogenic variants) in the alpha-tocopherol transfer protein (TTPA) gene.
Individuals usually show symptoms between 5 and 20 years of age. Symptoms and the severity of AVED may be different from person to person. Without treatment, symptoms may get worse as the person grows older.
AVED affects the brain and spinal cord (central nervous system or CNS) as well as the motor and sensory nerves that connect the CNS to the rest of the body (peripheral nervous system). This results in ataxia, which is difficulty controlling body movements and numbness of the hands and feet (peripheral neuropathy). Individuals with AVED develop increasing weakness of the legs, which may appear as an unsteady or staggering way of walking (gait) or trembling when standing still. If symptoms become very severe, an individual with AVED may require a wheelchair if they cannot walk.
Additional symptoms related to the CNS include loss of proprioception, which is an awareness of joint position in relation to other parts of the body. With time, reflexes in the legs may slow down or be absent (areflexia). Involvement of the throat muscles may lead to impaired swallowing or choking and may cause difficulty in eating. Slurred speech or difficulty speaking (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 the eyes. Retinitis pigmentosa (RP) is a large group of rare eye diseases that cause progressive degeneration of the membrane lining the eyes (retina). This results in visual impairment or decreased vision. Some affected individuals may have yellow “fatty” deposits (xanthelasma) in the retina.
Affected individuals may also develop sideways curvature of the spine (scoliosis), degenerative changes of the heart muscle (cardiomyopathy) or “fatty” deposits (xanthomas) affecting the Achilles tendon around the ankle. Some individuals with AVED may experience a form of dystonia. Dystonia is the name for a group of movement disorders generally characterized by involuntary muscle contractions that force the body into abnormal, sometimes painful, movements and positions (postures).
AVED is caused by changes (mutations or pathogenic variants) in the TTPA gene, which provides instructions to synthesize the alpha-tocopherol transfer protein (αTTP) . This protein controls the distribution and transportation of vitamin E from the liver to other cells and tissues throughout the body, including the brain. Individuals with AVED have non-working genes for TTPA and therefore, vitamin E cannot be properly distributed throughout the body especially to the brain where it is necessary for proper function. AVED is characterized by very low levels of vitamin E in the blood and tissues in the brain. Without normal levels of vitamin E in the tissues, an individual with AVED experiences damage to the body from lack of protection from damaging free radicals.
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 choleostasis (a syndrome of various causes characterized by impaired bile secretion), cystic fibrosis (primarily a lung disorder that results in choleostasis), primary biliary cirrhosis (a liver disorder that results in choleostasis) and abetalipoproteinemia (a digestive disorder characterized by fat malabsorption). Premature infants may have low vitamin E levels due to small amounts of vitamin E cross the placenta. In rare cases vitamin E deficiency may be caused due to poor diet. (For more information on the above disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
AVED is inherited, or passed down from parent to child, in an autosomal recessive manner. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working 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 non-working gene and, therefore, have a child with AVED is 25% with each pregnancy. The risk of having a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
AVED affects both males and females equally. The disorder is estimated to occur in fewer than 1 in 1,000,000 people. North African populations are most affected with AVED. Other cases have been reported in the Mediterranean region and Northern European countries. There have been cases in Asian countries such as Japan, China and the Philippines. The onset of AVED can occur during childhood or adulthood with cases reported ranging in children as young as 2 and adults as old as 52. Typically, the disease presents in individuals between ages 5 and 20 years. The disorder was first described in the medical literature in 1981.
A diagnosis of AVED is made 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 with no evidence of fat malabsorption and abnormalities in the TTPA gene).
Individuals with AVED are treated with high doses of vitamin E supplements. Early diagnosis and treatment can slow down or stop the progression of the disorder and in some people, even improve existing symptoms. Lifelong treatment with vitamin E will be needed.
Genetic counseling is recommended for affected individuals and their families.
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: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
For information about clinical trials sponsored by private sources, contact:
For information about clinical trials conducted in Europe, contact:
Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder (e.g., neurological disorders, Friedreich’s ataxia, cardiomyopathy, etc.)
Tabuena MD, Morigaki R, Miyamoto R, Mure H, Yamamoto N, Miyake K, Matsuda T, Izumi Y, Takagi Y, Tabuena RP, Kawarai T. Ataxia with vitamin E deficiency in the Philippines: A case report of two siblings. J Med Invest. 2021;68(3.4):400-403.doi: 10.2152/jmi.68.400
Zhang L, Zhang X, Lv P, Peng D. Clinical and genetic study of ataxia with vitamin E deficiency. 2021; doi: 10.21203/rs.3.rs-175944/v1
Zea Vera A, Liu W, Thomas C, Gilbert DL. Pearls & oy-sters: A novel presentation of ataxia with vitamin E deficiency caused by TTPA gene mutation. Neurology. 2021 Jan 26;96(4):e640-e642. doi: 10.1212/WNL.0000000000010853
Kohlschütter A, Finckh B, Nickel M, Bley A, Hübner C. First recognized patient with genetic vitamin E deficiency stable after 36 years of controlled supplement therapy. Neurodegener Dis. 2020;20(1):35-38. doi: 10.1159/000508080
Trotta E, Bortolotti S, Fugazzotto G, Gellera C, Montagnese S, Amodio P. Familial vitamin E deficiency: Multiorgan complications support the adverse role of oxidative stress. Nutrition. 2019 Jul-Aug;63-64:57-60. doi: 10.1016/j.nut.2018.11.012
Becker AE, Vargas W, Pearson TS. Ataxia with vitamin E deficiency may present with cervical dystonia. Tremor Other Hyperkinet Mov (N Y). 2016 May 17;6:374. doi: 10.7916/D8B85820
Bonello M, Ray P. A Case of ataxia with isolated vitamin E deficiency initially diagnosed as Friedreich’s ataxia. Case Rep Neurol Med. 2016;2016:8342653. doi: 10.1155/2016/8342653
Pearson TS. More than ataxia: hyperkinetic movement disorders in childhood autosomal recessive ataxia syndromes. Tremor and other hyperkinetic movements (New York, N.Y.) 2106;6: 368. doi:10.7916/D8H70FSS
Elkamil A, Johansen KK, Aasly J. Ataxia with vitamin E deficiency in Norway. J Mov Disord. 2015 Jan;8(1):33-6. doi: 10.14802/jmd.14030
El Euch-Fayache G, Bouhlal Y, Amouri R, Feki M, Hentati F. Molecular, clinical and peripheral neuropathy study of Tunisian patients with ataxia with vitamin E deficiency. Brain. 2014 Feb;137(Pt 2):402-10. doi: 10.1093/brain/awt339
Ulatowski L, Manor D. Vitamin E trafficking in neurologic health and disease. Annu Rev Nutr. 2013;33:87-103. doi: 10.1146/annurev-nutr-071812-161252
McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Ataxia with Vitamin E Deficiency. Entry Number; 277460: Last Edit Date 11/25/2013. https://omim.org/entry/277460 Accessed May 20, 2022.
Ataxia with Vitamin E Deficiency. Medline Plus. Updated Dec 1, 2015. Ataxia with vitamin E deficiency: MedlinePlus Genetics Accessed Jan 25, 2023.
Friedreich’s Ataxia Fact Sheet. National Institute of Neurological Disorders and Stroke. Updated Jul 25, 2022. https://www.ninds.nih.gov/friedreich-ataxia-fact-sheet. Accessed Jan 25, 2023.
Ataxia with vitamin E deficiency. Orphanet. Updated 2013 Feb https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=96. Accessed Jan 25, 2023.
Schuelke M. Ataxia with Vitamin E Deficiency. 2005 May 20 [Updated 2016 Oct 13]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1241/ Accessed Jan 25, 2023.
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/
Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/
This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/