Introduction:
Vitamin E, an antioxidant, protects cells in the body from the damaging effects of unstable molecules called free radicals. It also enhances immune function and prevents clogging in the arteries. The liver metabolizes and excretes the other forms of vitamin E, but it resecretes only alpha-tocopherol via the hepatic alpha-tocopherol transfer protein. Free radicals harm cells and may play a role in cancer and cardiovascular disease development.
How Bad Is Ataxia With Vitamin E Deficiency?
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A deficiency of vitamin E can lead to neurological problems such as difficulty coordinating movements (ataxia) and speech (dysarthria), loss of reflexes in the legs (lower limb areflexia), and a loss of sensation in the extremities (peripheral neuropathy).
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Some may also develop an eye disorder called retinitis pigmentosa that causes vision loss.
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Most people with ataxia, due to a vitamin E deficiency, start experiencing problems with movement between the ages of 5 and 15 years, which worsens with age.
What Are the Other Names for Ataxia With Vitamin E Deficiency?
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Ataxia with isolated vitamin E deficiency (AVED).
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Familial isolated vitamin E deficiency (FIVE).
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Friedreich ataxia phenotype with selective vitamin E deficiency.
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Friedreich-like ataxia.
How Common is the Disease?
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Ataxia with vitamin E deficiency is rare; however, its prevalence is unknown.
What is the Genetic Background of the Disease?
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Due to a mutation in both copies of the gene in each cell, this condition is inherited as an autosomal recessive pattern.
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An autosomal recessive condition is one in which one copy of the mutated gene is carried by each parent, who is asymptomatic in most cases.
What Are the Causes of Ataxia Due to Vitamin E Deficiency?
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Mutations in the TTPA gene cause ataxia with a vitamin E deficiency. This is because the TTPA gene provides instructions for making the α-tocopherol transfer protein (αTTP) found in the liver and brain.
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This protein regulates the distribution of dietary vitamin E (also known as α-tocopherol) throughout the body.
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Mutation of the TTPA gene impairs the activity of the αTTP protein, resulting in the inability to retain and use dietary vitamin E.
As a result,
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Free radicals build up inside the cells as the vitamin E levels in the blood are drastically reduced.
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Without vitamin E, nerve cells in the brain and spinal cord begin to degenerate because they are so susceptible to the harmful effects of free radicals.
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Movement issues and other ataxia-related symptoms can result from nerve cell damage.
What Are the Clinical Characteristics of AVED?
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The symptoms of ataxia with vitamin E deficiency (AVED) typically appear in late childhood or the beginning of adolescence between the ages of 5 to 15 years.
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The age of onset and disease course is more consistent within a given family. Still, symptoms and disease severity can differ even between siblings in families with different pathogenic variants.
The first symptoms include,
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Progressive ataxia (lack of coordination).
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The clumsiness of the hands (poor coordination, movement, or action).
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Loss of proprioception (reduction in the sense that includes the awareness of posture, weight, movement, and limb position about the environment).
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Areflexia (a condition in which your muscles do not respond to stimuli).
Other features include,
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Dysdiadochokinesia (inability to perform rapid, quick, synchronous, alternating muscle movements, including rotational forearm movement, fast finger tapping, opening and closing of the fists, foot tapping, etc.).
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Dysarthria (weakness in the muscles of speech, which causes slowed or slurred speech).
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Positive Romberg sign (inability to maintain an erect posture over 60 seconds with eyes closed).
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Head titubation (involuntary tremor of the head, neck, and trunk area).
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Positive Babinski sign (extension/ dorsiflexion /upward movement) of the big toe causing the fanning of the other toes).
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Macular atrophy (loss in the center of the field of vision).
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Retinitis pigmentosa (decreased vision at night or in low light and loss of side vision).
How to Diagnose Ataxia With Vitamin E Deficiency?
Suggestive Findings:
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Ataxia with vitamin E deficiency (AVED) should be suspected in individuals who typically present the symptoms mentioned above at the beginning of puberty.
Definitive Findings:
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There are currently no universal diagnostic standards for AVED.
The primary diagnostic indicator is the presence of
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A neurologic phenotype resembles Friedreich ataxia.
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A marked decreased plasma vitamin E (α-tocopherol) concentration.
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Standard lipoprotein profile in the absence of known causes of malabsorption of vitamin E.
Antenatal Diagnosis:
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Antenatal diagnosis is confirmed by identifying bi-allelic TTPA pathogenic variants via molecular genetic testing when the mutation has been identified in the family.
How to Manage Ataxia With Vitamin E Deficiency?
Treatment of Manifestations:
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Lifelong high-dose oral vitamin E supplementation to bring plasma vitamin E concentrations into the high-normal range.
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If the treatment starts at the early stage of the disease, it may, to some extent, reverse ataxia and mental deterioration.
Prevention of Primary Manifestations:
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Children with biallelic TTPA pathogenic variants who are presymptomatic can take vitamin E therapy to delay the onset of symptoms.
Genetic Counseling:
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Since AVED is inherited in an autosomal recessive manner, the parents of an affected child are obligate heterozygotes, carry one pathogenic variant, and are asymptomatic.
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Carrier detection for at-risk family members, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing can be done if the pathogenic variants in the family have been identified.
Surveillance:
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Check the level of plasma vitamin E every six months, especially in children.
Agents or Circumstances to Avoid:
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Smoking, occupations requiring quick responses, or good balance can be avoided.
Evaluation of Relatives at Risk:
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Evaluation for vitamin E deficiency, especially in the younger siblings of the person affected with the disease.
Others:
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People with AVED may find it challenging to ride a bicycle or operate a vehicle due to abnormal position sense in the extremities.
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A doctor should evaluate affected people before driving to check if they can safely operate a vehicle.
What is the Prognosis of Ataxia With Vitamin E Deficiency?
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If people are treated with vitamin E before the symptoms start, people with AVED can lead normal lives.
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Without treatment, individuals with AVED will become dependent on a wheelchair between the ages of 11 and 50 and may experience severe physical and mental problems.
Conclusion:
Ataxia with vitamin E deficiency (AVED) is a rare cause of hereditary ataxia in developing countries with an unknown prevalence. AVED is reversible if treated in time with vitamin E supplementation. In addition, vitamin E supplementation decreases the symptoms and prevents disease progression.
