Overview

What is ataxia?

Ataxia is a group of disorders that show abnormal coordination of muscle movement. It results from an unusual function in a part of the brain, which is called the cerebellum.¹ The cerebellum is involved in body movement control, balance, and speech processing.² Therefore, ataxia, a problem in the cerebellum, will affect coordination, balance, and speech. Symptoms are associated with the area of the brain affected, which patients with ataxia usually find difficulty in:³

• Balance and walking
• Speaking
• Swallowing
• Complex activities such as writing and eating
• Vision

What is vitamin E and its benefits?

Vitamin E is a fat-dissolving vitamin, which is found in fat-containing foods and naturally stored in human fat tissue. Therefore, normal people do not need to take vitamin E supplements. Vitamin E has antioxidant activities, maintaining healthy skin and eyes, and boosting the immune system to fight infection and illness. It inhibits the production of reactive oxygen species in oxidation reactions, and oxidation is related to various health conditions such as cancer, ageing, and arthritis. Various studies have shown that vitamin E is effective in the prevention of many diseases due to its role as an antioxidant involved in anti-inflammatory processes, platelet aggregation and boosting the immune system.⁴

Ataxia with vitamin E deficiency

What is Ataxia with vitamin E deficiency (AVED)?

Ataxia with vitamin E deficiency (AVED) is ataxia with a low level of vitamin E in the blood.⁵ This disorder is a rare case resulting from the mutation of the gene that produces the protein transferring vitamin E in the body. This causes the body not to retain and use vitamin E from diet. Low levels of vitamin E affect many parts of the body, especially the brain, spinal cord, eyes, and heart.⁵ AVED usually presents at the age of 5 to 20 or in late childhood or early teenagers.^5,6

What causes AVED?

Genetic mutations

AVED is a rare genetic disease resulting from a change in the alpha-tocopherol transfer protein (TTPA) gene or mutation of the TTPA gene, which gives instructions for producing TTPA protein. This protein controls the transportation of vitamin E from the liver to other cells throughout the body. Patients with AVED have a defect in this gene and vitamin E, which therefore cannot be transferred throughout the body, especially to the brain. Vitamin E cannot function properly, leading to a lack of antioxidant activities, the loss of which can damage the brain because of no protection from damaging free radicals.^5,6

Poor absorption of Vitamin E

People who have difficulty absorbing fat or fat-malabsorption disorders are more prone to vitamin E deficiency disorder than normal people because the absorption of vitamin E in the digestive tract relies on fat absorption.⁷ Vitamin E deficiency can happen after abnormal vitamin E absorption from fat, such as liver disorder, fat metabolism, or bile secretion impairment.⁵

What does vitamin E do in our body?

Antioxidant properties

Lipid peroxidation is a chemical reaction that leads to lipid degradation and follows by free radical formation. This reaction can damage cells, proteins, and DNA in the body. The antioxidant activity of vitamin E is to inhibit lipid peroxidation, reducing oxidative stress, which can damage cells and cause cell death.⁴

Maintaining nervous system health

As a role in antioxidant effects, vitamin E shows the effects of maintaining brain structure and function.⁸ In brain disorders such as Alzheimer’s disease, it could be hypothesised that free radicals that accumulate in the brain would damage neurones and lead to cognitive reduction and neurodegenerative diseases. Therefore, vitamin E could provide some protection.⁷

Impact on muscle function and overall coordination

Vitamin E can be found in muscles. Levels of vitamin E in muscle tissues can increase associated with the short duration of dietary intake or supplementation. Lack of vitamin E may cause muscle degradation, promote accumulation of fat, and increase oxidative stress.⁹ In eccentric exercise or strengthening exercise that induces muscular and oxidative damage, vitamin E supplementation can reduce oxidative stress and muscle damage.¹⁰

How is Ataxia related to AVED?

Neurological impact of Vitamin E deficiency

As Vitamin E is a strong antioxidant that helps prevent cells from oxidative stress, AVED mutation of the TTPA gene causes poor absorption of vitamin E, leading to no beneficial effects of vitamin E. This increases oxidative stress in the brain, which damages neurones and other cells. After resulting in neurodegeneration in the brain that controls movement and peripheral nerves, symptoms of ataxia are related to loss of coordination, muscle weakness, and peripheral neuropathy.⁶

What are the symptoms and diagnosis of AVED?

Common symptoms of AVED

AVED affects the brain and spinal cord, therefore, patients have symptoms similar to ataxia involved in body movement.

1. Progressive ataxia

Progressive ataxia is a group of rare neurological conditions such as Friedreich’s ataxia (FRDA). Ataxia is involved in a lack of coordination, including unsteady and imbalanced movement, clumsiness, and difficulty speaking. Patients with ataxia will have problems with gait (a pattern of walking) and balance. For some severe cases, patients may need to use a wheelchair if they cannot walk.¹¹

2. Dysarthria (speech difficulties)

Communication becomes more difficult, leading to speech disturbances. Dysarthria is difficulty speaking because muscles that are used for speaking are weak. Examples of dysarthria include:¹²

• The sound of speech is different
• Use strange words that are hard for others to understand
• Slurred speech
• Talking too fast or too slowly

3. Peripheral neuropathy

Peripheral neuropathy is numbness and tingling in your hands and feet because nerves at the hands, feet, and arms are injured.¹³

How do you know you have AVED?

Diagnosis, or the process of identifying AVED, is a physical examination, clinical evaluation, patient history, and various tests such as detecting vitamin E plasma dosage, lipids without causes of malabsorption, and genetic testing for an abnormal TTPA gene.^5,14 In the starting stages of this disorder, neuroimaging does not clearly identify abnormality of the cerebellum.¹⁴ Electromyography measuring muscle response will tell a pure sensory neuronopathy. Molecular analysis will confirm the diagnosis.¹⁴

Moreover, eye and heart examinations are also performed. Consultation with clinical genetics is provided in the evaluation of patients with AVED to inform them that this is an inherited disease and the importance of taking life-long vitamin E supplementation that can prevent patients and their families from having the symptoms.⁶ Summary of method in diagnosing AVED:⁶ 

• Checking clinical symptoms
• Laboratory examination
• Electrophysiological examination
• Neuroimaging
• Microscopic examination

Treatment and management

As it is a life-long treatment, the management aims to reduce a life span and improve quality of life by enhancing movement and speech.

Vitamin E supplementation

As the disease lacks vitamin E, the first-line treatment is taking a high dose of vitamin E supplement. If people start this treatment early, it can slow the progression of the disorder. However, this is a long-term treatment, and it takes time to recovery.⁶ Vitamin E should be taken daily. The recommended doses range from 800 mg/day to 1500 mg/day or 40 mg/kg per day in children.

After being treated, the likely outcome of the disease is not fully recovered, and in some cases, patients may need to use wheelchairs.¹⁴ However, the duration of recovery depends on the timing of supplementation and the onset age of losing vitamin E.⁶

Some evidence supports that starting vitamin E supplements early in the disease can improve symptoms of ataxia and mental decline.¹⁵

Symptomatic treatment

1. Physical therapy for coordination and strength

Physiotherapy will improve the movement of your arms and legs and prevent muscle weakness and a fixed shortening of muscles resulting in being stuck in one position (contractures).³ Physical therapy is a tailored exercise programme to strengthen and stretch your muscles.³

2. Occupational therapy for daily living skills

Occupational therapists will teach you how to deal with gradual loss of mobility and provide new skills to cope with daily activities, for example, how to use a wheelchair and other devices.³

3. Speech and language therapy (SLT) to improve communication and swallowing

SLT will help train individuals to improve a motor speech disorder that changes the quality of their voice, clarity, and nature of speaking.¹⁵ Many studies show that individually tailored training such as breathing support and speech rate can improve speech disorder.¹⁵

Long-term care

After starting vitamin E treatment, a regular vitamin E check-up is required every 6 months. Patients with AVED will be treated by a multidisciplinary team, who will take care of the patient’s plan involving various departments, including a neurologist, physiotherapist, nurse, and others.³ Along with the plan, patients require regular assessment of physical, social, and psychological activities. The plan will be adjusted depending on the progression of the disease.³

How to live with AVED

As AVED is usually found in children, patients with AVED need particular support and self-discipline. Supporting patients themselves and their families by providing education and awareness as well as managing treatment planning will help patients and their families understand thoroughly this lifelong treatment and enhance patient compliance. Along with emotional support, it provides counselling to deal with the patient's emotional and psychological challenges.

Summary

Ataxia with vitamin E deficiency (AVED) is a rare genetic disease that lacks vitamin E due to mutation. Ataxia can come from many causes. Therefore, to differentiate from other ataxia, the level of vitamin E in the blood should be measured and there should be no sign of fat malabsorption. The management will require lifelong high-dose vitamin E supplementation and other symptomatic treatment. Vitamin E can provide benefits to symptoms and prevent the disease progression.