Ataxia with vitamin E deficiency

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

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. A shortage (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). Some people with this condition have developed an eye disorder called retinitis pigmentosa that causes vision loss. Most people who have ataxia with vitamin E deficiency start to experience problems with movement between the ages of 5 and 15 years. The movement problems tend to worsen with age.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

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 and family implications

From: MedlinePlus Genetics, National Library of Medicine

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.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

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

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal pyramidal sign · Very frequent (99-80%)

Functional neurological abnormalities related to dysfunction of the pyramidal tract.

Areflexia · Very frequent (99-80%)

Absence of neurologic reflexes such as the knee-jerk reaction.

Ataxia · Very frequent (99-80%)

Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).

Babinski sign · Very frequent (99-80%)

Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.

Low levels of vitamin E · Very frequent (99-80%)

A reduced concentration of vitamin E in the blood circulation. Vitamin E is a lipophilic vitamin that is also known as alpha-tocopherol.

Muscle weakness · Very frequent (99-80%)

Reduced strength of muscles.

Peripheral neuropathy · Very frequent (99-80%)

Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.

Abnormality of speech or vocalization · Frequent (79-30%)

An abnormality in the sound (volume) or cadence (rate) of speech.

Cerebellar atrophy · Frequent (79-30%)

Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.

Clumsiness · Frequent (79-30%)

Lack of physical coordination resulting in an abnormal tendency to drop items or bump into objects.

Dysarthria · Frequent (79-30%)

Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.

Dysdiadochokinesis · Frequent (79-30%)

A type of ataxia characterized by the impairment of the ability to perform rapidly alternating movements, such as pronating and supinating his or her hand on the dorsum of the other hand as rapidly as possible.

Dysmetria · Frequent (79-30%)

A type of ataxia characterized by the inability to carry out movements with the correct range and motion across the plane of more than one joint related to incorrect estimation of the distances required for targeted movements.

Gait disturbance · Frequent (79-30%)

The term gait disturbance can refer to any disruption of the ability to walk.

Other findings in the same source

From: Orphanet

Additional reported features include Head titubation (Frequent (79-30%)); Impaired proprioception (Frequent (79-30%)); Nyctalopia (Frequent (79-30%)); Nystagmus (Frequent (79-30%)); Pes cavus (Frequent (79-30%)); Scoliosis (Frequent (79-30%)); Sensory neuropathy (Frequent (79-30%)); Abnormality of retinal pigmentation (Occasional (29-5%)); Abnormality of visual evoked potentials (Occasional (29-5%)); Arrhythmia (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Ataxia with vitamin E deficiency is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Ataxia with vitamin E deficiency. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.