Postmortem study of ataxia with retinitis pigmentosa by mutation of the alpha-tocopherol transfer protein gene

J Neurol Neurosurg Psychiatry. 2000 Apr;68(4):521-5. doi: 10.1136/jnnp.68.4.521.

Abstract

A new syndrome of ataxia and retinitis pigmentosa with vitamin E deficiency caused by the missense mutation of alpha-tocopherol transfer protein (alpha-TTP) gene was recently proposed. After studying the first postmortem case with this mutation pathologically and biochemically, whether the symptoms can be treated by supplementation of vitamin E or not is discussed. The major pathological findings were retinal atrophy; severe dying back-type degeneration of the posterior column; and massive accumulation of lipofuscin in neurons including dorsal root ganglion (DRG) cells, which were almost identical to those in vitamin E deficient animals and patients with fat malabsorption. Also, mild loss of Purkinje cells was noted. Because robust expression of alpha-TTP was detected in the cerebellum as well as in the liver and the tissue concentration of vitamin E in the cerebellum was still low even after oral supplementation, the mild Purkinje cell loss might be related to the mutant alpha-TTP in the cerebellum. By contrast, in the DRG, thought to be mainly responsible for ataxia, no expression of alpha-TTP was detected, and the tissue concentration of vitamin E increased to normal after supplementation. It is therefore considered that oral supplementation of vitamin E should effectively counteract the progression of ataxia.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Ataxia / genetics*
  • Ataxia / pathology*
  • Carrier Proteins / genetics*
  • Humans
  • Male
  • Mutation / genetics
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / pathology*

Substances

  • Carrier Proteins
  • alpha-tocopherol transfer protein