Abstract

Mutations in the butyrylcholinesterase enzyme (BChE) can result in prolonged duration of action of the neuromuscular blocking agents, succinylcholine and mivacurium, as BChE hydrolyses these drugs. Hereditary low BChE activity can cause extensively prolonged apnoea during general anaesthesia when these drugs are used. The aim of this study was to describe novel mutations in the butyrylcholinesterase gene (BCHE) in patients who have experienced prolonged duration of action of mivacurium or succinylcholine. The Danish Cholinesterase Research Unit registers patients with prolonged duration of action to succinylcholine and mivacurium. Patients were studied if they had equivocal phenotypes on the basis of BChE activity, biochemical inhibitor reactions and with pedigree if possible. Complete nucleotide sequencing was performed to describe the genotype and pedigree was used to separate the alleles. Multiple sequence alignment of BChE was performed for comparison with other species. Genotyping indicated seven novel mutations in the BCHE (I373T, G467S, W518R, L184S, V421A, M462I and R577H). We have found seven new variants of the BCHE, which seem to reduce the activity of BChE in patients undergoing anaesthesia involving succinylcholine or mivacurium.

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