Transketolase abnormality in tolazamide‐induced Wernicke's encephalopathy

Abstract

We studied a thiamine-dependent enzyme, transketolase, from fibroblasts of a diabetic patient who developed Wernicke's encephalopathy when treated with tolazamide, in order to delineate if this patient also had transketolase abnormality [high Km for thiamine pyrophosphate (TPP)], as previously reported in postalcoholic Wernicke-Korsakoff syndrome. In addition to this patient, we also studied this enzyme from three diabetic kindreds without any history of Wernicke's encephalopathy and from four normal controls. We found that the above-mentioned patient and one of the diabetic kindreds with no history of Wernicke's encephalopathy had abnormal transketolase as determined by its Km for TPP. These data suggest a similarity between postalcoholic Wernicke-Korsakoff syndrome and the patient with tolazamide-induced Wernicke's encephalopathy from the standpoint of transketolase abnormality.

Transketolase abnormality in cultured fibroblasts from familial chronic alcoholic men and their male offspring.

“…and enzymes (18), a reduction in the synthesis ofNADPH would result in decreased GSH and thus seriously impair the function of several cerebral metabolic pathways. The earliest well documented change in thiamine deficiency is a decrease in transketolase activity (19,20) and a fall in erythrocyte and myocardial GSH (21 and Gibson (7 (26). The present biochemical observations on the occurrence of transketolase abnormality predominantly in familial chronic alcoholic males and their sons are striking in that these children had no prior history of alcohol abuse.…”