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Friedreich‐like ataxia with retinitis pigmentosa caused by the His 101 Gln mutation of the α‐Tocopherol transfer protein gene
Author(s) -
Yokota Takanori,
Shiojiri Toshiaki,
Gotoda Takanari,
Arita Makoto,
Arai Hiroyuki,
Ohga Tatsuhide,
Kanda Takashi,
Suzuki Junichi,
Imai Tomihiro,
Matsumoto Hiroyuki,
Harino Seiyo,
Kiyosawa Motohiro,
Mizusawa Hidehiro,
Inoue Keizo
Publication year - 1997
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410410621
Subject(s) - retinitis pigmentosa , ataxia , vitamin e deficiency , medicine , endocrinology , retinal degeneration , vitamin e , biology , retinal , ophthalmology , biochemistry , psychiatry , antioxidant
The α‐tocopherol transfer protein (α‐TTP) is a cytosolic liver protein that is presumed to function in the intracellular transport of α‐tocopherol, the most biologically active form of vitamin E. We studied 4 unrelated patients with autosomal recessive Friedreich‐like ataxia who had isolated vitamin E deficiency. A point mutation was identified in all of them at position 101 of the gene for α‐TTP, where histidine (CAT) was replaced with glutamine (CAG). Three of the 4 patients developed retinitis pigmentosa subsequent to the onset of ataxia. Neurological symptoms included ataxia, dysarthria, hyporeflexia, and decreased proprioceptive and vibratory sensations. Electrophysiological and pathological examinations showed that the cardinal sites affected were the central axons of dorsal root ganglion cells and the retina, with minor involvement of the peripheral sensory nerve, optic nerve, and pyramidal tract. The vitamin E tolerance test performed showed that the absorption of vitamin E was normal but that its decrease from the serum was accelerated. Oral administration of vitamin E appeared to halt the progression of visual and neurological symptoms. We propose a new treatable syndrome of Friedreich‐like ataxia and retinitis pigmentosa caused by a defect in the α‐TTP gene.