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Pseudocholinesterase Deficiency

Practice Essentials

Pseudocholinesterase deficiency is an inherited enzyme abnormality that results in abnormally slow metabolic degradation of exogenous choline ester drugs such as succinylcholine and mivacurium. If there is a  deficiency in the plasma activity of pseudocholinesterase, prolonged muscular paralysis may occur, resulting in the extended need for mechanical ventilation.A variety of pathologic conditions, physiologic alterations, and medications also can lower plasma pseudocholinesterase activity.

A personal or family history of an adverse drug reaction to one of the choline ester compounds, such as succinylcholine, mivacurium, or cocaine, may be the only clue suggesting pseudocholinesterase deficiency. Most clinically significant causes of pseudocholinesterase deficiency are due to one or more inherited abnormal alleles that code for the synthesis of the enzyme.

This condition is recognized most often when respiratory paralysis unexpectedly persists for a prolonged period of time following administration of standard doses of succinylcholine.
The mainstay of treatment in these cases is ventilatory support until diffusion of succinylcholine from the myoneural junction permits return of neuromuscular function of skeletal muscle. The diagnosis is confirmed by a laboratory assay demonstrating decreased plasma cholinesterase enzyme activity.

Genetic analysis may demonstrate a number of allelic mutations in the pseudocholinesterase gene, including point mutations resulting in abnormal enzyme structure and function and frameshift or stop codon mutations resulting in absent enzyme synthesis. Partial deficiencies in inherited pseudocholinesterase enzyme activity may be clinically insignificant unless accompanied by a concomitant acquired cause of pseudocholinesterase deficiency. Clinically significant effects  are generally not observed until the plasma cholinesterase activity is reduced to less than 75% of normal.
 Pseudocholinesterase deficiency is most common in people of European descent; it is rare in Asians.

Prognosis for recovery following administration of succinylcholine is excellent when medical support includes close monitoring and respiratory support measures. In nonmedical settings in which individuals with pseudocholinesterase deficiency are exposed to cocaine, sudden cardiac death can occur.

The main complication resulting from pseudocholinesterase deficiency is the possibility of respiratory failure secondary to succinylcholine or mivacurium-induced neuromuscular paralysis. Individuals with pseudocholinesterase deficiency may also be at increased risk of toxic reactions, including sudden cardiac death, associated with recreational use of cocaine. Patients with known pseudocholinesterase deficiency may wear a medic-alert bracelet that will notify healthcare workers of increased risk from administration of succinylcholine. These patients also may notify others in their family who may be at risk for carrying one or more abnormal pseudocholinesterase gene alleles.

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