Medical Genetics - V. M. Zaporozhan 2005

Multifactorial Diseases
Pharmacogenetics
Examples of Pharmacogenetic Reactions — Hypersensitivity to Dithylin

Hypersensitivity to ditilin occurs due to a mutation in the serum cholinesterase enzyme. This enzyme hydrolyzes Muscle relaxants (ditilin, suxamethonium, and other agents with curariform action) that are widely used in surgical practice. Upon administration of ditilin or its analogs, immobilization and respiratory arrest occur for 2-5 minutes; subsequently, ditilin is broken down into Choline and succinic acid, which lack curariform activity. The activity of the abnormal serum cholinesterase is 4 times lower than that of the normal enzyme, which leads to a drastic decrease in The rate of ditilin Hydrolysis and results in prolonged apnea in patients.

The Synthesis of the enzyme is determined by several allelic Variants of the Gene. The CHE^U_I gene determines the synthesis of the normal enzyme; CHE^I_D determines the synthesis of an enzyme with reduced activity and is the most common allele. In individuals homozygous for this gene, ditilin is not metabolized, and the patient can be saved following ditilin administration only by switching to Artificial ventilation and urgent transfusion of fresh Blood containing the enzyme. About 3-4% of the European population are heterozygous carriers of the mutant gene. The frequency of clinically significant homozygotes for this gene in the European population is 1:3500.