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

A new syndrome of ataxia and retinitis pigmentosa with vitamin E deficiency caused by the missense mutation of á-tocopherol transfer protein (á-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 á-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 á-TTP in the cerebellum. By contrast, in the DRG, thought to be mainly responsible for ataxia, no expression of á-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 eVectively counteract the progression of ataxia. (J Neurol Neurosurg Psychiatry 2000;68:521–525)