Mukherjee A B, Svoronos S, Ghazanfari A, Martin P R, Fisher A, Roecklein B, Rodbard D, Staton R, Behar D, Berg C J
J Clin Invest. 1987 Apr;79(4):1039-43. doi: 10.1172/JCI112916.
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.
我们研究了一种硫胺素依赖性酶——转酮醇酶，该研究涉及41名人类受试者的培养成纤维细胞，其中包括酒精中毒相关韦尼克 - 科萨科夫综合征患者（n = 3）、家族性慢性酒精中毒男性（n = 7）、他们的儿子（n = 7）、非酒精性男性（n = 7）、他们的男性后代（n = 7）以及一个无任何酒精中毒病史的阿米什家族的三代成员（n = 10）。本研究旨在确定转酮醇酶异常（即硫胺素焦磷酸的米氏常数（Km）较高），此前在韦尼克 - 科萨科夫综合征患者中报道的这种异常，在无酒精滥用病史但有酒精中毒高风险的家族性慢性酒精中毒男性及其儿子中是否普遍存在。我们的数据表明，一种先天性缺陷（即转酮醇酶对硫胺素焦磷酸的Km较高），易引发与韦尼克 - 科萨科夫综合征中报道的类似的硫胺素缺乏疾病，可能在普通人群中发生。然而，由于某些尚未解释清楚的原因，这种变异似乎在无任何酒精中毒病史的家族性慢性酒精中毒男性及其男性后代中更频繁地出现。正如之前所提示的，从阿米什家族谱系研究中揭示的这种酶变异的遗传模式可能是常染色体隐性遗传。
