We have investigated a
thiamine-dependent
enzyme,
transketolase, in cultured fibroblasts from 41 human subjects, including patients with
alcoholism-associated
Wernicke-Korsakoff syndrome (n = 3), familial chronic alcoholic males (n = 7), their sons (n = 7), nonalcoholic men (n = 7), their male offspring (n = 7), and three generations of an Amish family (n = 10) without any history of
alcoholism. This study was undertaken to delineate whether
transketolase abnormality (i.e., high Michaelis Menton constant (Km) for
thiamine pyrophosphate), previously reported in patients with
Wernicke-Korsakoff syndrome is prevalent among familial chronic alcoholic men and their sons without prior history of
alcohol abuse but who are at high risk for
alcoholism. Our data suggest that an inborn error (i.e., high Km of
transketolase for
thiamine pyrophosphate) predisposing to
thiamine deficiency diseases similar to those reported in
Wernicke-Korsakoff syndrome may occur in the general population. However, for some as yet unexplained reason(s) this variant seems to occur more frequently among familial chronic alcoholic men and their male offspring without any history of
alcoholism. The inheritance pattern of this
enzyme variant as revealed from an Amish pedigree study may be autosomal recessive as previously suggested.