Case study- Wernicke-Korsakoff syndrome

Case details

A 58-year-old man with a history of heavy drinking presents with confusion, unstable gait, and nystagmus. A provisional diagnosis of Wernicke’s- Korsakoff syndrome is made. Which of the patient’s enzymes of the pentose phosphate pathway is inhibited due to vitamin deficiency in this case?

A. Transaldolase

B. Transketolase

C. Glucose-6-P- dehydrogenase

D. Epimerase

E. Phosphogluconate dehydrogenase

The correct answer is B. – Transketolase.

Wernicke-Korsakoff syndrome (thiamine deficiency) is often associated with chronic alcoholics. Thiamine deficiency is uncommon except in alcoholics as a result of nutritional deficiencies and malabsorption. The term Wernicke’s encephalopathy is used to describe the clinical triad of confusion, ataxia, and nystagmus (or ophthalmoplegia). When persistent learning and memory deficits are present, the symptom complex is often called Wernicke-Korsakoff syndrome. Clinically, this term is best conceptualized as 2 distinct syndromes with acute/sub acute confusional state and often reversible findings of Wernicke’s encephalopathy versus persistent and irreversible findings of Korsakoff dementia.

Heavy, long-term alcohol use is most commonly associated with Wernicke-Korsakoff syndrome. Within 2-3 weeks of decreased intake and thiamine depletion, areas of the brain with the highest thiamine content and turnover will demonstrate cellular impairment and injury.

A deficiency in thiamine will decrease the efficiency of the enzymes for which TPP is required as a cofactor namely, PDH complex, alpha ketoglutarate dehydrogenase complex, Alpha ketoacid dehydrogenase complex and the activity of Tryptophan pyrrolase.

A deficiency in thiamine also adversely affects the flux of glucose metabolized by the pentose phosphate pathway. Transketolase activity requires the cofactor TPP to transfer the glycoaldehyde unit from a ketose to an aldose in the remodeling reactions of the pathway. When these reactions cannot proceed, precursor metabolites build up, and the flow through the pathway is decreased. This results in a decreased production of NADPH and decreased conversion of glucose to pentose, including ribose. This can lead to decreased regeneration of reduced glutathione and susceptibility to oxidative stress.

Transketolase is the only TPP (Thiamine pyrophosphate) dependent enzyme in the list. The reaction catalyzed by Transketolase is shown in the figure


Figure- Reaction catalyzed by Transketolase. TPP is required as a coenzyme for this reaction.

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