CHAPTER 33: Disturbances in Acetyl-CoA Metabolism: A Key Factor in Preclinical and Overt Thiamine Deficiency Encephalopathy

Overt and subclinical forms of thiamine deficits are common in underdeveloped regions of the world, but are not rare in population groups at risk in apparently developed countries. Thiamine deficiency depresses the activities of pyruvate and ketoglutarate dehydrogenase complexes which are key steps in providing acetyl-CoA and in controlling the yield of the tricarboxylic acid cycle and energy production in the brain mitochondria, respectively. The reduction in acetyl-CoA levels in mitochondrial and cytoplasmic compartments in these conditions are responsible for loss of vulnerable neurons and suppression of their transmitter functions, respectively. Cholinergic neurons are particularly susceptible to thiamine deficit-evoked shortages of acetyl-CoA due to its use both for energy production and acetylcholine synthesis. Therefore, national wide or individual actions as well as early identification of asymptomatic cases of thiamine deficiency are undertaken to prevent the irreversible consequences of this pathology. Alcoholics, children, elderly and disabled people are those at risk of thiamine deficiency. The detection of subclinical thiamine deficiency in these pre-selected groups by determination of blood thiamine diphosphate level, erythrocyte transketolase or serum γ-glutamyl transpeptidase activity, in combination with dedicated questionnaires, may be a good tool for screening in the early stages of this pathology.