Skip to
  1. Homepage
  2. Rare diseases
  3. Search
Simple search

Simple search

(*) mandatory field


Other search option(s)

Ataxia with vitamin E deficiency

Synonym(s) AVED
Ataxia with isolated vitamin E deficiency
Familial isolated vitamin E deficiency
Friedreich-like ataxia
Isolated vitamin E deficiency
Prevalence 1-9 / 1 000 000
Inheritance Autosomal recessive
Age of onset All ages
  • G11.1
  • C1848533
  • C535393
  • 10047631


Ataxia with vitamin E deficiency (AVED) is a neurodegenerative disease belonging to the inherited cerebellar ataxias. It is mainly characterized by progressive spino-cerebellar ataxia, loss of proprioception, areflexia, and is associated with a marked deficiency in vitamin E.

Global prevalence is not known but population-based studies have been performed and prevalence can be extrapolated at approximately 1/300,000. AVED is the second most frequently inherited cerebellar ataxia in North Africa. As vitamin E deficiency might bring protection against malaria (see this term), it could explain a higher prevalence of AVED in Plasmodium infested areas.

AVED presents generally between ages 5 and 20 years with variable phenotype and severity. Progressive spino-cerebellar ataxia, areflexia and loss of proprioception, mainly in distal joint position and of vibration sense, induce a noticeable clumsiness and imbalance. Patients may have a characteristic head titubation. Tendon reflexes are dramatically reduced and extensor plantar reflexes are frequent. Cerebellar impairment frequently manifests as dysmetria, dysdiadochokinesia and dysarthria. Decreased visual acuity with retinitis pigmentosa may be seen. In some cases, disease onset is late (> 30 years) and the course is milder. On the contrary, in early-onset cases, the course is more severe, with an increased risk of cardiomyopathy. Overall, the clinical picture of AVED is close to that of Friedreich's ataxia (see this term).

AVED is caused by mutations in the tocopherol (alpha) transfer protein gene (TTPA; 8q13). This protein binds alpha-tocopherol (a vitamin E isomer) and very-low-density lipoproteins (VLDLs) in the liver. When mutated, TTPA prevents vitamin E linking to VLDLs, preventing it to pass into general circulation. Many mutations have been identified, but p.His101Gln and c.744delA are respectively responsible for the late-onset/mild and early-onset/severe forms of the disease.

Diagnosis is based on physical examination, on vitamin E plasma dosage and on exclusion of known causes of malabsorption. Laboratory findings reveal a very marked deficiency of vitamin E in plasma but normal levels of lipid and lipoprotein profiles. Neuroimaging does not show an obvious cerebellar atrophy in the first stages of the disease. Electromyography usually reveals a pure sensory neuronopathy (ganglionopathy). Molecular analysis confirms the diagnosis.

Differential diagnosis mainly includes Friedreich ataxia, sensory ataxic neuropathy with dysarthria and ophthalmoplegia (SANDO) and abetalipoproteinemia (see these terms). Other autosomal recessive cerebellar ataxias may be considered as well (Refsum disease, ataxia telangiectasia, Charcot-Marie-Tooth disease 1A and ataxia with oculomotor apraxia types 1 and 2 (see these terms)).

Antenatal diagnosis is feasible via molecular genetic testing when the mutation has been identified in the family.

The disease has an autosomal recessive mode of inheritance, with a subsequent recurrence risk of 25%.

Treatment is based on a lifelong high-dose vitamin E supplementation, which should be taken every day. When treated early, some symptoms could be reversible; in older patients disease progression can be slowed. It remains unknown whether in families of index cases vitamin E preventive treatment can be administered in presymptomatic individuals to prevent development of AVED.

Even if treated, patients frequently have a poor prognosis and become wheelchair bound within 8 and 20 years of age.

Expert reviewer(s)

  • Dr Mathieu ANHEIM

(*) Required fields.

Attention: Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed.

Captcha image

Detailed information

Summary information
Review article
Clinical genetics review
Get Acrobat Reader
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.