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

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 68; no. 4; pp. 521 - 525
• Main Authors: Yokota, T, Uchihara, T, Kumagai, J, Shiojiri, T, Pang, J J, Arita, M, Arai, H, Hayashi, M, Kiyosawa, M, Okeda, R, Mizusawa, H
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.04.2000; BMJ; BMJ Group
• Subjects: Aged; ataxia; Ataxia - genetics; Ataxia - pathology; Biological and medical sciences; Carrier Proteins - genetics; Errors of metabolism; Humans; Male; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Mutation - genetics; retinitis pigmentosa; Retinitis Pigmentosa - genetics; Retinitis Pigmentosa - pathology; Short Report; vitamin E; α-tocopherol transfer protein; Human; Nervous system diseases; Retinitis pigmentosa; Deficiency; Postmortem; Metabolic diseases; Male; α-Tocopherol; E-Vitamins; Cerebral disorder; Case study; Pathology; Gene; Central nervous system disease; Ataxia; Diagnosis; Mutation; Neurological disorder; Elderly
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp.68.4.521

A new syndrome of ataxia and retinitis pigmentosa with vitamin E deficiency caused by the missense mutation of α-tocopherol transfer protein (α-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 α-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 α-TTP in the cerebellum. By contrast, in the DRG, thought to be mainly responsible for ataxia, no expression of α-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.