Response to mivacurium in a patient compound heterozygous for a novel and a known silent mutation in the butyrylcholinesterase gene: genotyping by sequencing.


BACKGROUND:Patients who are homozygous for the atypical mutation, compound heterozygous for atypical and silent mutations, or homozygous for silent mutations (SS) respond to mivacurium with extensively prolonged neuromuscular block. Although important, exact phenotyping of these patients is difficult. This article presents the pharmacodynamics and pharmacokinetics of a normal dose of mivacurium in a patient with phenotype SS, including a pedigree analysis and delineation of the molecular genetic method used to identify the genotype. METHODS:The neuromuscular block following administration of mivacurium, at a dose of 0.14 mg/kg, was monitored in a 30-yr-old healthy man with use of a mechanosensor and mechanomyography, and times to different levels of recovery were measured. Venous samples for determination of the mivacurium isomers were collected during the interval 134-494 min after administration of mivacurium, and the terminal half-lives were calculated. Butyrylcholinesterase activity, phenotype, and genotype were determined for both the patient and the family. Complete nucleotide sequencing was used to identify the genotype. RESULTS:A train-of-four ratio of 0.75 was reached 469 min after the injection of mivacurium. The terminal elimination half-lives of the mivacurium isomers, cis-trans and trans-trans, were 90 min. Complete nucleotide sequencing revealed two point mutations, the known silent variant S7 and a previously undescribed mutation of amino acid residue 170 introducing a stop codon. CONCLUSIONS:The patient was compound heterozygous for silent mutations in the butyrylcholinesterase gene. The response to mivacurium was an extensively prolonged duration of action. Identification of the rare silent mutations presupposes access to modern molecular genetic methods such as complete nucleotide sequencing.






Gätke MR,Ostergaard D,Bundgaard JR,Varin F,Viby-Mogensen J




Has Abstract


2001-09-01 00:00:00












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