Butyrylcholinesterase (BCHE) genotyping for post-succinylcholine apnea in an Australian population

Background: Measurement of plasma butyrylcholinesterase (BChE) activity and inhibitor-based phenotyping are standard methods for identifying patients who experience post-succinylcholine (SC) apnea attributable to inherited variants of the BChE Enzyme. Our aim was to develop PCR-based assays for BChE mutation detection and implement them for routine diagnostic use at a university teaching hospital.

Methods: Between 1999 and 2002, we genotyped 65 patients referred after prolonged post-SC apnea. Five BChE gene mutations were analyzed. Competitive oligo-priming (COP)-PCR was used for flu-1, flu-2, and K-variant and direct DNA Sequencing analysis for dibucaine and sil-1 mutations. Additional DNA Sequencing of BChE coding regions was provided when the five-mutation screen was negative or mutation findings were inconsistent with Enzyme activity.

Results: Genotyping identified 52 patients with primary hypocholinesterasemia attributable to BChE mutations, and in 44 individuals the abnormalities were detected by the five-mutation screen (detection rate, 85%). Additional Sequencing studies revealed mutations in eight other patients, including five with novel mutations. The most common genotype abnormality was compound homozygous dibucaine and homozygous K-variant mutations. No simple homozygotes were found. Of the remaining 13 patients, 3 had normal BChE activity and gene, and 10 were diagnosed with hypocholinesterasemia unrelated to BChE gene abnormalities.

Conclusion: A five-mutation screen for investigation of post-SC apnea identified BChE gene abnormalities for 80% of a referral population. Six new BChE mutations were identified by Sequencing studies of 16 additional patients.