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

A new syndrome of ataxia and retinitis pigmentosa with vitamin E deficiency caused by the missense mutation of alpha-tocopherol transfer protein (alph a-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 maj or pathological findings were retinal atrophy; severe dying back-type degen eration of the posterior column; and massive accumulation of lipofuscin in neurons including dorsal root ganglion (DRG) cells, which were almost ident ical to those in vitamin E deficient animals and patients with fat malabsor ption. Also, mild loss of Purkinje cells was noted. Because robust expressi on 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 t o be mainly responsible for ataxia, no expression of alpha-TTP was detected , and the tissue concentration of vitamin E increased to normal after suppl ementation. It is therefore considered that oral supplementation of vitamin E should effectively counteract the progression of ataxia.