From the Guidelines
Acetylcholinesterase (AChE) deficiency is not a recognized medical condition, but rather, AChE inhibition can occur due to exposure to organophosphate (OP) pesticides, which can have severe neurodevelopmental effects, particularly in children and fetuses, even at levels below that required to cause AChE inhibition. The effects of AChE inhibition due to OP pesticide exposure can be severe and long-lasting, including neurodevelopmental deficits, cognitive impairments, and behavioral problems 1. These effects can occur even in the absence of overt poisoning, and the developmental deficits may not manifest until months or years later.
The scientific consensus is that AChE inhibition is uninformative with regard to neurodevelopmental effects in children, and that the toxic effects from chronic, low-level exposure occur at concentrations too low to inhibit cholinesterase 1. Other effects, such as neuroinflammation, protein-kinase C receptor signaling, insulin resistance, dopaminergic and glutamatergic neurotransmission, and interference with DNA synthesis and nuclear transcription factor functioning, may mediate the OP toxicity to neuronal systems, leading to childhood behavioral and cognitive deficits 1.
Some of the key effects of AChE inhibition due to OP pesticide exposure include:
- Neurodevelopmental deficits, such as reduced IQ, attention deficits, and memory problems
- Cognitive impairments, such as decreased mental development and reasoning
- Behavioral problems, such as ADHD and social cognition deficits
- Neuroanatomic alterations, such as changes in brain volume in regions responsible for attention, receptive language processing, social cognition, and regulation of inhibition 1
It is essential to note that these effects can be permanent and may emerge from further follow-up of those exposed in early life. Therefore, it is crucial to minimize exposure to OP pesticides, particularly during pregnancy and early childhood, to prevent these severe and long-lasting effects.
From the Research
Effects of Acetylcholinesterase (AChE) Deficiency
- AChE deficiency can lead to congenital myasthenic syndromes, a heterogeneous collection of genetic disorders of neuromuscular transmission characterized by fatiguable muscle weakness 2.
- Patients with AChE deficiency can experience severe weakness, respiratory crises, and other symptoms, and may require treatment with anticholinesterase medication and other therapies 3, 4.
- Treatment with anticholinesterase medication, such as pyridostigmine, can improve muscle strength and reduce symptoms, but may have diminishing efficacy over time 2.
- The addition of β2-adrenergic receptor agonists, such as salbutamol, to anticholinesterase medication can improve muscle fatigue, neuromuscular transmission, and synaptic structure, and may counteract the detrimental effects of long-term acetylcholinesterase inhibitors 2, 3.
- Other treatments, such as 3,4-diaminopyridine, may also be effective in improving muscle strength and reducing symptoms in patients with AChE deficiency 5.
- Pseudocholinesterase enzyme deficiency, a related condition, can lead to prolonged apnea and paralysis following administration of certain muscle relaxant drugs, and requires careful diagnosis and management 6.