[Familial Wernicke's-like encephalopathy].

Wernicke's encephalopathy is a syndrome characterized by ataxia, ophthalmoplegia, and confusion with thiamine deficiency. We reported on two Japanese brothers with a newly discovered recessively inherited syndrome similar to Wernicke's encephalopathy that developed in the second decade of life; this syndrome was manifested clinically as thiamine-responsive diplopia, ataxia and confusion without serum thiamine deficiency. The patients had complex partial seizure. The administration of high-dose thiamine improved these symptoms. MRI of the brain showed high-intensity signals in the bilateral medial thalamus and periaqueductal region on fluid-attenuated inversion recovery images; these signals were characteristic of findings in Wernicke's encephalopathy. There was no history of chronic alcoholism. The clinical and images features resembling Wernicke's encephalopathy in these patients suggested that the syndrome was caused by a genetic disorder of thiamine metabolism. Genomic analysis of SLC10A3 encoding human thiamine transporter 2 revealed that the patients were compound heterozygotes for the K44E and E320Q mutations. Gene-expression analyses of mammalian culture cells showed that intracellular thiamine uptake activities were decreased significantly. High expression of SLC19A3 RNA in the thalamus may explain the selective thalamic lesions on MRI. The identification of this syndrome proves insight into the thiamine metabolism associated with Wernicke's encephalopathy in humans.