Ataxia with vitamin E deficiency

Synonyms

5

Overview

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

Symptoms

  • Abnormal pyramidal signs
  • Gait disturbance
  • Incoordination
  • Muscle weakness
  • Peripheral neuropathy
  • Severe vitamin E deficiency
  • Ataxia
  • Reduced reflexes
  • Loss of proprioception
  • Increased serum cholesterol level

Causes

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. This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations.

Absorption of vitamin E depends on normal pancreatic biliary function, biliary secretion, micelle formation, and penetration across intestinal membranes. Interference with any of these processes could result in a deficiency state. Cystic fibrosis, abetalipoproteinemia, chronic cholestatic hepatobiliary disease, short-bowel syndrome, and isolated vitamin E deficiency syndrome are all potential causes of a deficiency state.

Prevention

Genetic counseling may determine whether your children are at risk for this disease.

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.

Prognosis

The disorder will continue to progress, although slowly. Complete blindness is uncommon.

Treatment

There is no effective treatment for this condition. Wearing sunglasses to protect the retina from ultraviolet light may help preserve vision. Controversial studies have suggested that treatment with antioxidants (such as vitamin A palmitate) may slow the disease from getting worse.

Resources

  • Genetics Home Reference
  • NIH