AVED Fact Sheet
Ataxia:
AVED (Ataxia with Vitamin E Deficiency)
RELATED GENES:
TTPA
MUTATION TYPE:
TTPA -> Pathogenic variants
LAST UPDATE:
09/23/2025 by Marcio Galvão
LOCATION:
Chromosome 8 (8q12.3)
HERITAGE:
Autosomal Recessive
Content generated with the support of Generative AI, reviewed by the author.
1. ABOUT AVED
Ataxia with Vitamin E Deficiency (AVED) is a progressive disease that affects motor control and movement. VDA is caused by mutations in the TTPA gene located on chromosome 8 (Ref. [1] ).
The TTPA gene in the nucleus of liver cells (liver cells) contains the instructions for synthesizing (producing) a protein called αTTP (alpha-tocopherol transfer protein). This protein captures vitamin E and transports it from the liver to other cells and tissues in the body, including the brain.
In individuals with AVED, due to the gene defect, this protein is not synthesized properly, which prevents vitamin E from being distributed properly. The result is very low vitamin E levels in the blood and brain tissue.
Figure 1 - Generated with the support of Artificial Intelligence
Although vitamin E is found in a variety of foods, people with CVAD are unable to properly retain and utilize the vitamin E they obtain from their diet. Vitamin E is crucial because it acts as an antioxidant, protecting nervous system cells (neurons) from damage caused by molecules called "free radicals." Thus, people with CVAD experience damage to various body systems due to a lack of adequate protection against free radicals, which are harmful to cells. CVAD was first described in the medical literature in 1981 [1] .
Note that in addition to primary deficiency due to a mutation in the TTPA gene, vitamin E deficiency can also be a secondary manifestation of various disorders that impair the absorption of vitamin E from fats, such as liver disorders, fat metabolism disorders, and bile secretion disorders. Some of these disorders include cholestasis, cystic fibrosis, primary biliary cirrhosis, and abetalipoproteinemia. Furthermore, deficiency may occur in premature newborns due to small amounts of vitamin E crossing the placenta. It is also possible (though rare) for vitamin E deficiency to be caused by inadequate diets [1] .
2. TYPICAL SYMPTOMS
AVED is a multisystem disease , which means it can affect different systems of the human body, such as the central nervous system (brain and spinal cord), the cardiovascular system (heart) and also the eyes (retina) [1] .
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Without adequate levels of vitamin E, individuals with AVED develop neurological problems typical of ataxias , such as difficulty coordinating movements, slurred speech (dysarthria), difficulty swallowing (dysphagia), loss of reflexes in the legs (areflexia in the lower limbs) and loss of sensation in the limbs (peripheral neuropathy). *
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It is also possible to experience loss of proprioception, which is the ability to recognize the location of the body (its position and orientation in space) and the relative position of each part of the body in relation to the others, without using vision.
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Individuals with stroke may develop increasing weakness in their legs, which may manifest as an unsteady gait or tremors when standing. If stroke symptoms become severe, the individual may need a wheelchair if they can no longer walk.
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Eye problems associated with Retinitis Pigmentosa (RP) can arise, a condition that causes progressive degeneration of the retina, affecting vision.
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Disorders affecting the heart muscles (cardiomyopathy) and abnormal curvature of the spine (scoliosis) may also occur. Because of these and other symptoms, AVED is quite similar to Friedreich's ataxia , making differential diagnosis important.
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Some individuals with AVED may experience a form of dystonia (involuntary muscle contractions that force the body into abnormal positions or movements that can sometimes be painful).
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Intellect and emotions are rarely affected. However, source [2] reports that "psychotic episodes and intellectual decline have been reported in some individuals," and that "rarely, academic performance in some individuals may decline due to loss of intellectual abilities."
For more information on symptoms, see the "Clinical Characteristics" section of the GeneReviews source [2] .
3. ONSET
Symptoms of stroke can appear in childhood or adulthood, with cases reported ranging from children as young as 2 years old to adults as old as 52. Typically, individuals with stroke experience symptoms between the ages of 5 and 20 [1]. Symptoms can vary from person to person and vary in severity (including among siblings within the same family). Without proper treatment, symptoms tend to worsen as a person gets older.
Note: GeneReviews [2] indicates that the onset of symptoms of AVED is generally "between 5 and 15 years of age." This same source reports that the age of onset of symptoms and the risk of certain symptoms may vary depending on the pathogenic variant of the TTPA gene. For example, the p.His101Gln variant has been associated with later onset of symptoms (after 30 years of age) and a higher risk of retinopathies, and this variant is typically reported in individuals of Japanese descent. The c.744delA pathogenic variant of the TTPA gene is associated with earlier onset of symptoms and greater severity of the disease, as well as a slightly increased risk of cardiomyopathies. This variant is most frequently found in individuals of Mediterranean and North African descent. There are other possible pathogenic variants of the TTPA gene that can cause AVED.
4. ANTICIPATION
Anticipation is not observed in AVED, given that the disease "skips generations".
5. INHERITANCE
AVED is inherited as an autosomal recessive trait. This means that an individual only develops symptoms if they inherit two mutated copies (alleles) of the TTPA gene (one from their biological father and one from their mother). If they inherit only one copy of the mutant gene (from either father or mother), they will not develop the disease, but will instead be a carrier of the mutant gene. In carriers (i.e., those who have only one mutated allele of the TTPA gene), the "normal" copy of the gene takes precedence over the defective copy, and therefore, carriers do not develop symptoms . In individuals who inherit two defective copies (pathogenic variants) of the TTPA gene, the disease will manifest at some point in their lives (see Section 3. Age of Symptoms ).
Probability of children inheriting the disease
Statistically, if both parents are carriers:
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The probability of each of the children developing the disease (= inheriting one mutant allele from the mother and another from the father) is 25% .
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The probability of each of the children not developing the disease and also becoming a carrier (= inheriting only one copy (allele) with the gene mutation, either from the father or the mother) is 50% .
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The probability of each child not inheriting any mutant allele (neither from the father nor from the mother) and not developing the disease nor becoming an asymptomatic carrier is 25% .
Genetic counseling
Given that inheritance is hereditary (it can be passed down to future generations), once a pathogenic variant of the TTPA gene has been identified in a family member, genetic counseling is recommended for both individuals affected by AVED and their families. This includes discussions, for example, about prenatal testing to identify genetic mutations for those diagnosed with or at risk for AVED and wishing to have children. This is a personal and ethically sensitive issue, but it is advisable to at least discuss the matter with a neurologist or geneticist.
Notes: "Autosomal" means the gene is located on any chromosome except the X and Y sex chromosomes. Genes, like chromosomes, typically exist in pairs (we have a pair of each gene; one copy of the gene is inherited from the mother, the other from the father). Thus, men and women are equally likely to inherit a mutated gene that can cause hereditary ataxia. "Recessive" means that two mutated copies (alleles) of the gene must be inherited (one from the biological father, the other from the mother) for a person to develop the disease.
Figure 2 - Source: MedlinePlus, US National Library of Medicine .
6. PREVALENCE
Although the exact global prevalence is not known, population studies suggest a prevalence of approximately 1 in 300,000 individuals [8] . Populations in North Africa appear to be most affected by AVED.
7. ADDITIONAL INFORMATION
The diagnosis of AVED is made through a rigorous clinical examination, evaluation of the patient's history, and a variety of tests looking for characteristic findings, such as low blood vitamin E levels, with normal lipoprotein and lipid levels, and no evidence of fat absorption problems. The diagnosis can be confirmed by molecular genetic testing that identifies biallelic mutations in the TTPA gene. For more information on genetic testing for pathogenic variants of the TTPA gene that can cause AVED, see [2] .
Notes
1 - Many symptoms of AVED are similar to those of Friedreich's Ataxia (FA) , therefore differential diagnosis (genetic testing to rule out FA) is important [1, 4].
2 - Imaging tests (brain magnetic resonance imaging) in patients with AVED may reveal cerebellar atrophy (according to [2] , present in approximately half of affected individuals).
8. THERAPIES AND DRUGS IN TRIALS FOR AVED
There are still no medications and therapies approved by the FDA (United States) and ANVISA (Brazil) specifically to cure AVED, but in many cases it is possible to eliminate symptoms with vitamin E supplementation (see Section 9. Treatments ).
Information about clinical trials of therapies and medications for AVED can be found at www.clinicaltrials.gov
9. TREATMENTS
Individuals with AVED (Ataxia with Vitamin E Deficiency) are treated with high doses of vitamin E supplements. Early diagnosis and proper treatment can slow down or even halt disease progression in some individuals, and may also improve existing symptoms. Treatment must be continued throughout life [1]. It is important to note that vitamin E supplementation should be done under medical supervision to avoid the risk of overdose [6].
The GeneReviews source [2] states that “when vitamin E treatment is initiated in asymptomatic individuals (e.g., younger siblings of a diagnosed person), AVED symptoms may not develop.” For this reason, early diagnosis of AVED is important. Additionally, depending on clinical manifestations, individuals with AVED should be followed by a multidisciplinary team of specialists, such as neurologists, psychiatrists, physical therapists, orthopedic doctors, nutritionists, and others.
Smoking is not recommended for patients with AVED (as it reduces blood levels of vitamin E).
Below are some best practices for managing ataxia symptoms in AVED:
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Neurofunctional physiotherapy, exercise (especially stationary cycling), and other regular physical activities (such as yoga, Pilates, water aerobics, etc.) are recommended—within each person’s individual capabilities.
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To reduce the risk of falls due to balance difficulties while walking, assistive devices such as canes, walkers, or wheelchairs may be adopted depending on the disease stage.
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Occupational therapy and some home and lifestyle adaptations can help (e.g., installing grab bars in hallways and bathrooms, using a shower chair, placing night lights, rearranging furniture to facilitate mobility, removing rugs to prevent tripping, using lidded cups with straws, wearing non-slip and easy-to-wear shoes, etc.).
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Rest whenever necessary, and ensure good quality nighttime sleep. In case of sleep difficulties, consult a physician, as some medications may help (e.g., Cannabidiol oil).
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In addition to vitamin E supplementation, maintain a healthy diet and adequate hydration.
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It is advisable to manage body weight to prevent further mobility challenges.
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Consult a neuro-ophthalmologist if visual symptoms appear.
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For dysarthria, if present, speech therapy is recommended. Depending on the stage of the disease, assistive communication devices (available for smartphones, computers, iPads, etc.) may be considered.
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For dysphagia, if it occurs, consultation with a speech-language pathologist is also advised—there are exercises that can help improve swallowing and reduce the risk of aspiration pneumonia.
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In the case of dystonia, consult a neurologist to determine the most appropriate medication.
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If needed, medications for anxiety and depression are available. Consult a physician to assess the most suitable options.
See information about medications for ataxia symptoms.
See information about treatments and care for patients.
See information about those with a recent diagnosis.
See information about Support Groups for patients and caregivers.
10. REFERENCES
The references below include academic sources and specialized organizations that supported the information in this fact sheet, including peer-reviewed articles, genetic repositories (OMIM), literature summaries (GeneReviews), and informational materials from ataxia foundations. For more information, see the ataxia.info References list .
Ref #1
Fonte:
NORD ®
Copyright © 2024 NORD – National Organization for Rare Disorders, Inc.
Language:
English
Date:
Last updated: 03/23/2023
Ref #2
Source:
Markus Schuelke, MD.
Copyright © GeneReviews. GeneReviews ® is a registered trademark of the University of Washington, Seattle.
Language:
English
Date:
Last Update: March 16, 2023.
Ref #3
Fonte:
GARD - Genetic and Rare Diseases Information Center.
Copyright © National Center for Advancing Translational Sciences - National Institutes of Health (NIH).
Language:
English
Date:
Last Updated: January 2024
Ref #4
Fonte:
NEUROMUSCULAR DISEASE CENTER (Alan Pestronk, MD)
Washington University, St. Louis, MO - USA
Language:
English
Date:
Last Updated: Please see https://neuromuscular.wustl.edu/rev.htm
Ref #5
Source:
OMIM ® - An Online Catalog of Human Genes and Genetic Disorders.
Copyright © Johns Hopkins University.
Language:
English
Date:
Edit History: joanna: 02/04/2022
Ref #6
Source:
Alexander Zubkov, MD, PhD Integrative Neurologist
YouTube
Language:
English
Date:
Dec 1, 2022
Ref #7
Source:
Mathieu ANHEIM
Orphanet
Language:
English
Date:
Jan 2, 2021