Individual susceptibility to Wernicke-Korsakoff syndrome and alcoholism-induced cognitive deficit: impaired thiamine utilization found in alcoholics and alcohol abusers.
To investigate mechanisms predisposing to alcoholic brain damage, thiamine (vitamin B1 ), riboflavin (vitamin B2 ) and pyridoxine (vitamin B6 ) status was compared in persistent alcohol misusers (PAM) admitted for detoxification without evidence of significant brain damage, in alcoholics known to have severe chronic brain damage (BDAM), and in age, gender and ethnicity matched controls. Thus, activities of thiamine-dependent transketolase (ETK), riboflavin-dependent glutathione reductase, and pyridoxine-dependent aspartate amino transferase were assayed, together with the enzyme activities following addition of the appropriate co-factor. Twenty per cent of the PAM group had an abnormally low ETK activity and an abnormally high activation ratio, while 45% were abnormal in either one or both parameters. An additional 10% of the PAM group had an abnormally high activation ratio but normal ETK activity, as did 30% of the BDAM group. These subgroups of alcohol misusers may have increased requirements for thiamine secondary to an abnormality of the transketolase protein that may predispose such patients to alcoholic brain damage. There was no evidence of riboflavin or pyridoxine deficiency in either of the patient groups. We conclude that thiamine deficiency was commonly present in the alcoholic patients, and that a subgroup of patients may be predisposed to more severe brain damage as a consequence of abnormalities in the transketolase protein.
Heap
Laura C
LC
Department of Clinical Biochemistry, Kings College School of Medicine and Dentistry, London, UK.
Pratt
Oliver E
OE
Ward
Roberta J
RJ
Waller
Seta
S
Thomson
Allan D
AD
Shaw
G Ken
GK
Peters
Timothy J
TJ
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000503:physiopathology; D000437:Alcoholism / Q000235:genetics*; D001925:Brain Damage, Chronic / Q000209:etiology / Q000235:genetics; D003072:Cognition Disorders / Q000209:etiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D020915:Korsakoff Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D013831:Thiamine / Q000378:metabolism*; D014174:Transketolase / Q000378:metabolism; D006113:United Kingdom; D044465:White People
D014174:Transketolase; D013831:Thiamine