Ataxia with vitamin E deficiency

Definition

Ataxia with vitamin E deficiency (AVED) is a progressive disease affecting motor control and movement.

Alternate names

• AVED
• Ataxia with isolated vitamin E deficiency
• Familial isolated deficiency of vitamin E
• Friedreich-like ataxia with selective vitamin E deficiency
• Familial isolated vitamin E deficiency
• Friedreich-like ataxia; Isolated vitamin E deficiency

Descritption

Ataxia with vitamin E deficiency is a disorder that impairs the body's ability to use vitamin E obtained from the diet. Vitamin E is an antioxidant, which means that it protects cells in the body from the damaging effects of unstable molecules called free radicals.

Epidemiology

Ataxia with vitamin E deficiency is a rare condition; however, its prevalence is unknown.

Cause

Mutations in the TTPA gene cause ataxia with vitamin E deficiency. The TTPA gene provides instructions for making the α-tocopherol transfer protein (αTTP), which is found in the liver and brain. This protein controls distribution of vitamin E obtained from the diet (also called α-tocopherol) to cells and tissues throughout the body. Vitamin E helps cells prevent damage that might be done by free radicals.

TTPA gene mutations impair the activity of the αTTP protein, resulting in an inability to retain and use dietary vitamin E. As a result, vitamin E levels in the blood are greatly reduced and free radicals accumulate within cells. Nerve cells (neurons) in the brain and spinal cord (central nervous system) are particularly vulnerable to the damaging effects of free radicals and these cells die off when they are deprived of vitamin E. Nerve cell damage can lead to problems with movement and other features of ataxia with vitamin E deficiency.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Signs and symptoms

• Symptoms of AVED include slurred speech (dysarthria), difficulty coordinating movements (ataxia), numbness in the hands and feet (peripheral neuropathy), and progressive leg weakness.
• Some affected individuals may experience vision loss due to damage to the back of the eye (retinitis pigmentosa).
• Symptoms typically begin during childhood or adolescence and worsen with age, resulting in the need for a wheelchair by early adulthood.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Abnormal pyramidal sign
• Areflexia(Absent tendon reflexes)
• Muscle weakness(Muscular weakness)

30%-79% of people have these symptoms

• Dysarthria(Difficulty articulating speech)
• Dysdiadochokinesis(Difficulty performing quick and alternating movements)
• Dysmetria(Lack of coordination of movement)
• Gait disturbance(Abnormal gait)
• Nyctalopia(Night blindness)
• Nystagmus(Involuntary, rapid, rhythmic eye movements)
• Pes cavus(High-arched foot)
• Scoliosis
• Sensory neuropathy(Damage to nerves that sense feeling)

5%-29% of people have these symptoms

• Abnormality of retinal pigmentation
• Abnormality of visual evoked potentials
• Arrhythmia(Abnormal heart rate)
• Developmental regression(Loss of developmental milestones)
• Diabetes mellitus
• Dystonia
• Hemiplegia/hemiparesis(Paralysis or weakness of one side of body)
• Hypertonia
• Hypertrophic cardiomyopathy(Enlarged and thickened heart muscle)
• Mental deterioration(Cognitive decline)
• Skeletal muscle atrophy(Muscle degeneration)
• Tremor
• Visual impairment(Impaired vision)

Diagnosis

AVED may be suspected in individuals who have the following findings at the beginning of puberty:

• Progressive ataxia
• Clumsiness of the hands
• Loss of the ability to know where one's body is in space (proprioception)
• Absent reflexes (areflexia)
• The inability to perform rapid, alternating movements (dysdiadochokinesia)
• A tendency to sway or fall while standing upright with the feet together, arms stretched out and the eyes closed (positive Romberg sign)
• A nodding movement of the head (titubation)
• Decreased visual sharpness (acuity)
• Positive Babinski sign (upward movement of the big toe and fanning of the feet after the sole of the foot has been firmly stroked)
• Macular atrophy (wasting away of the cells that form the part of our eye responsible for central vision)
• Retinitis pigmentosa (eye disease in which there is damage to the retina)

Laboratory studies typically show a reduced plasma vitamin E concentration but normal levels of lipoproteins (proteins that combine with and transport fat or other lipids in the blood). Other studies that may be useful include: nerve conduction studies, brain imaging, and studies of nerve tissues.

Although no universal diagnostic guidelines are available, researchers suggest that diseases that cause fat malabsorption, such as abetalipoproteinemia should be ruled out. Genetic testing finding two TTPA gene mutations may be useful to confirm the diagnosis.

Treatment

Treatment for AVED requires lifelong high dose supplementation of vitamin E. When treated early, some symptoms, such as ataxia and intellectual decline, can be reversed. In older patients, treatment may slow disease progression, but some symptoms remain.<ref>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; 1993-2020. Available from: https://www.ncbi.nlm.nih.gov/books/NBK97260/</ref>[1].

References

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NIH genetic and rare disease info

• NIH info on Ataxia with vitamin E deficiency

Ataxia with vitamin E deficiency is a rare disease.

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