Vitamin E Deficiency Ataxia (AVED): Causes, Symptoms, and Treatment

Ataxia with Vitamin E Deficiency (AVED) is a rare autosomal recessive disorder caused by mutations in the TTPA gene (α-tocopherol transfer protein), leading to severe vitamin E malabsorption.

Pathophysiology

• α-TTP normally incorporates vitamin E into VLDL for systemic distribution.
• Mutations → no functional α-TTP → vitamin E not secreted by liver → plasma levels undetectable.
• Vitamin E is a lipid-soluble antioxidant; its absence causes oxidative damage to neuronal membranes, especially in cerebellum and posterior columns.

Clinical Presentation (Onset 2–20 yrs)

• Progressive ataxia (gait, limbs), dysarthria, loss of proprioception/vibration.
• Areflexia, Babinski signs, skeletal deformities (pes cavus, scoliosis).
• Retinitis pigmentosa, cognitive decline in some.
• Normal serum lipids (distinguishes from abetalipoproteinemia).

Diagnosis

• Undetectable plasma α-tocopherol (<0.5 mg/dL) with normal lipids.
• Genetic testing: TTPA mutations (chr8q13).
• MRI: cerebellar atrophy, hyperintensity in posterior columns.

Treatment

• High-dose oral vitamin E: 800–1500 mg/day (RRR-α-tocopherol) lifelong.
• Early initiation halts progression; may improve ataxia if started before severe neuropathy.
• Monitor levels, LFTs, coagulation (vitamin E has antiplatelet effect).
• Genetic counseling for family.

Differential

Friedreich ataxia (frataxin mutation, onset <25, cardiomyopathy, diabetes), abetalipoproteinemia (acanthocytes, fat malabsorption), ataxia-telangiectasia, REFsum disease.

AVED is treatable—early diagnosis prevents irreversible disability.