Prolonged paralysis due to low butyrylcholinesterase (BChE) activity after suxamethonium administration arises from either an inherited or an acquired deficiency, but the risk of prolonged paralysis is dependent on both enzyme activity and genotype. BCHE is a highly polymorphic gene, and the prevalences of the different mutations show large geographic and ethnic variation. The terminology can be challenging (1). Biochemical phenotypes are defined by the pattern of values obtained after differential enzyme inhibition to determine “inhibitor numbers,” e.g., the dibucaine number (DN). The most accurate identification of phenotype uses 3 inhibitors, typically dibucaine plus fluoride and the carbamate Ro 02-0683 (2), which allow identification of such phenotypes as AK and AF, as well as the original Atypical (A) and UA phenotypes, and improves the extrapolation of phenotype to genotype.
Low DN values normally indicate the A phenotype (DN typically 20–30), which is demonstrated only by homozygotes for the defining Asp70Gly mutation (A/A genotype) or by its compound heterozygotes with a silent variant mutation (A/S genotype)—the silent variant gene product contributing little to the total. At very low enzyme activity, little significance can be placed on the DN; imprecision at these levels prevents its accurate determination. A very low DN should be thought of as pointing neither to a “silent” phenotype nor to an A phenotype, a conclusion supported in this case by the fact that the genotype results do not show the Asp70Gly mutation. In cases in which inhibitor numbers can be determined accurately, the presence of a silent variant in heterozygotes is masked by the phenotype of the other allele. That has been demonstrated in regard to a heterozygote for the Arg386Cys mutation described here, which demonstrated a “Usual” phenotype, as well as for other U/S and compound heterozygotes.
This case shows the value of genotyping in a case of low BChE activity, because identifying a genetic cause may have repercussions for other family members.
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Authors' Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
- Received for publication July 12, 2011.
- Accepted for publication July 14, 2011.
- © 2012 The American Association for Clinical Chemistry