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A disorder caused by atypical or deficiency of
pseudocholinesterase (PCE) leading to prolonged paralysis after
administration of succinylcholine or mivacurium.
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Pseudocholinesterase Deficiency; Plasma Cholinesterase
Deficiency; Butyrylcholinesterase Deficiency; Cholinesterase II Deficiency;
Succinylcholine Sensitivity; Suxamethonium Sensitivity.
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For homozygosity, the incidence is approximately
1:2,000-4,000, whereas the incidence for heterozygosity increases to up to
1:500. The gene for the dibucaine-resistant atypical cholinesterase appears
to be widely distributed. Among Caucasians, males are affected almost twice
as often as females. The frequency for heterozygosity is low among black
people, Japanese and non-Japanese Orientals, South Americans, Australian
aborigines, and Arctic Inuits (in general). However, there are a few Inuit
populations (e.g., Alaskan Inuits) with an unusually high gene frequency for
PCE deficiency. A relatively high frequency also was reported among Jews
from Iran and Iraq, Caucasians from North America, Great Britain, Portugal,
Yugoslavia, and Greece.
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Autosomal recessive. Genes encoding
cholinesterase 1 (CHE1) and CHE2 have been mapped to 3q26.1-q26.2. One gene
is silent, whereas the other is responsible for the defect in
cholinesterase.
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The inherited defect is caused by either the
presence of an atypical PCE or complete absence of the enzyme.
Cholinesterases are enzymes that facilitate hydrolysis of the esters of
choline. Acetylcholine, the most commonly encountered of these esters, is
the mediator of the whole cholinergic system. Acetylcholine is immediately
inactivated “in situ” by a specific acetylcholinesterase in the ganglions
of the autonomic nervous system (preganglionic and postganglionic in the
parasympathetic nervous system and almost exclusively preganglionic in the
sympathetic nervous system), in the synapses of the central nervous system,
and in the neuromuscular junctions. The affinity of PCE is lower for
acetylcholine, but higher for other esters of choline, such as
butyrylcholine, benzoylcholine, and succinylcholine, and for aromatic
esters (e.g., procaine, chloroprocaine, tetracaine). Normal PCE is produced
in the liver, has a plasma half-life of 8 to 12 days, and can be found in
plasma, erythrocytes, glial tissue, liver, pancreas, and bowel. When
succinylcholine is used for anesthesia, its high plasma concentration
immediately after intravenous injection decreases rapidly in normal
individuals because of the rapid action of plasma PCE. In case of an
atypical PCE or complete absence of PCE, the effect of the injected
succinylcholine can last for up to 10 hours.
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The disorder is completely asymptomatic prior to the use
of succinylcholine. The diagnosis is suspected in any patient with prolonged
paralysis (>10 minutes) after succinylcholine administration. A nerve
stimulator helps confirm the diagnosis by demonstrating the flaccidity of
hand muscles. Laboratory tests use the property of the local anesthetic dibucaine, which can inhibit normal PCE activity in vitro, but has minimal effects
on atypical enzymes. Normal PCE activity is reduced by nearly 80%,
whereas the activity of atypical enzymes is reduced by only 20%. This
defines the “dibucaine number” (DN), which represents the percentage
inhibition of PCE by a fixed concentration of dibucaine under standardized
conditions using benzoylcholine as the substrate. DN ...