A 6-month-old infant presents with constipation, poor feeding, ptosis, dilated sluggish pupils, and descending flaccid paralysis. The mother reports feeding the infant honey. The toxin involved acts by which mechanism?

• A Competitive antagonism at postsynaptic nicotinic receptors
• B Irreversible inhibition of acetylcholinesterase
• C Blockade of presynaptic voltage-gated calcium channels
• D Proteolytic cleavage of SNARE proteins, preventing acetylcholine vesicle fusion with the presynaptic membrane ✓

Explanation

Botulinum toxin is a zinc-dependent endopeptidase that cleaves components of the SNARE complex, chiefly SNAP-25, syntaxin, and synaptobrevin (VAMP). Vesicle docking and fusion with the presynaptic terminal membrane fail, so calcium entry can no longer trigger acetylcholine release, producing a flaccid, descending paralysis. Blockade of presynaptic calcium channels is the mechanism in Lambert-Eaton syndrome, and irreversible acetylcholinesterase inhibition produces fasciculations and excess secretions rather than hyposecretion.

Reference: Guyton and Hall Textbook of Medical Physiology, 14th ed.

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