Abstract
We report on two previously healthy 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, ptosis, gait ataxia, and disturbance of consciousness without serum thiamine deficiency. The administration of high-dose thiamine improved the symptoms within a few weeks. There was no history of chronic alcoholism in either patient. Magnetic resonance imaging 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. Genomic analysis of SLC19A3 encoding human thiamine transporter 2 (hTHTR2) revealed that the patients were compound heterozygotes for the K44E and E320Q mutations. Gene-expression analyses of mammalian culture cells showed intracellular thiamine uptake activity was decreased significantly. The identification of this syndrome showed a thiamine-dependent state and provides insight into the thiamine metabolism associated with Wernicke's encephalopathy in humans.
