From the Research
Acetylcholinesterase (AChE) deficiency leads to excessive acetylcholine accumulation in synapses, causing overstimulation of cholinergic receptors throughout the body, resulting in a cholinergic crisis characterized by increased secretions, bronchospasm, bradycardia, hypotension, muscle weakness, fasciculations, and potentially respiratory failure. This condition can occur genetically or more commonly from exposure to AChE inhibitors like organophosphate pesticides or nerve agents 1. The underlying mechanism involves the critical role of AChE in breaking down acetylcholine in synapses - when this enzyme is deficient, neurotransmitter levels remain elevated, causing continuous stimulation of both muscarinic and nicotinic receptors throughout the peripheral and central nervous systems, disrupting normal neurotransmission and autonomic function.
Clinical Presentation
The clinical presentation of AChE deficiency can vary depending on the severity and cause of the deficiency. Some common symptoms include:
- Increased secretions
- Bronchospasm
- Bradycardia
- Hypotension
- Muscle weakness
- Fasciculations
- Potentially respiratory failure
Treatment
Treatment of AChE deficiency focuses on removing the cause (if exogenous) and administering atropine to block muscarinic effects and pralidoxime (2-PAM) at 1-2g IV initially followed by 500mg/hr infusion to reactivate the enzyme in cases of poisoning 2. Supportive care including respiratory support, fluid management, and seizure control is essential.
Recent Findings
Recent studies have identified new inhibitors of AChE, such as tilorone, which has been shown to be a potent and selective inhibitor of the enzyme 1. This has potential implications for the treatment of neurological disorders like Alzheimer's disease, Lewy body dementia, and Parkinson's disease dementia, as well as other conditions like myasthenia gravis and anticholinergic poisoning.
Key Points
- AChE deficiency can occur genetically or from exposure to AChE inhibitors
- The condition results in a cholinergic crisis characterized by overstimulation of cholinergic receptors
- Treatment focuses on removing the cause and administering atropine and pralidoxime
- Supportive care is essential to manage symptoms and prevent complications
- Recent studies have identified new inhibitors of AChE, which may have potential therapeutic applications 1.