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Transketolase abnormality in tolazamide-induced Wernicke's encephalopathy

Section on Developmental Genetics, Human Genetics Branch (Drs. Mukherjee, Ghazanfari, and Svoronos), National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD; and the Laboratory of Theoretical and Physical Biology (Mr. Staton), NICHD, and the Department of Neurology (Drs. N akada and K wee), University of California, Davis, Veterans Administration Medical Center, Martinez, CA.

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 K_M 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 K_M 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.

Address correspondence and reprint requests to Dr. Mukherjee, NIH, Building 10, Room 8C429. Bethesda, MD 20892.

Accepted for publication March 12, 1986.

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