Mutations in the BCHE1 gene
lead to variant enzyme forms with changed substrate behavior,
reduced activity, or the absence of the enzyme
butyrylcholinesterase. This plasma enzyme hydrolyses
acetylcholine, propionylcholin, butyrylcholin and exogenous cholin
ester-containing drugs such as the muscle relaxants suxamethonium
(succinylcholin) and mivacurium, and ester-type local anesthetics
like procain. It also acts as a scavenger against organophosphorus
and carbamate compounds of pesticides like parathion13),
chemical warfare agents like Sarin and narcotics like cocain and
Butyrylcholinesterase is attributed a function in the neural
system, its precise role however is still subject of research. The
homozygous BCHE K-variant has been associated with early onset
Alzheimer disease 6). The association of BCHE genotypes
with Alzheimer disease susceptibility or development as well as
cognitive functions in general is discussed 14, 15).
BCHE1 on chromosome 3q26.1-q26.2 encodes a 602 amino acid protein
including a 28 amino acid leader peptide. The enzyme is composed
of 4 identical subunits of 574 amino acids, each containing an
active catalytic site. The gene is located on 4 exons of which one
autosomal recessive condition called
deficiency is asymptomatic in the absence of exogenous cholin
ester-containing drugs and chemical compounds. Homozygous or
compound heterozygous carriers of BCHE mutations can remain
unrecognized until an adverse response to cholin ester-compounds
occurs as in postanesthetic apnea or pesticide and cocain
persons carrying BCHE mutations and
undergoing surgical anesthesia, the combination with cholin
ester-containing muscle relaxants can lead to prolonged
post-anesthetic apnea requiring respiratory support due to a
slower or absent enzymatic degradation of the muscle relaxant and
continued neuromuscular blockade.
Apnea after suxamethonium injection normally lasts approximately 5
min. In BCHE mutation carriers, apnea can last from 10 min to 2 or
3 hours depending on the patient’s genotype.
measuring the inhibition of the enzymatic activity in the presence
or absence of the specific inhibitors dibucain and sodium
fluoride, three main BCHE genotypes have been recognized:
Qualitative variants like the
2) that show less inhibition with dibucain or
fluoride than the normal genotype.
Quantitative variants like the
J 4) and
showing reduced enzymatic activity.
“silent” genotypes, like
silent 1, showing
absent or extremely reduced (<10%) enzymatic activity.
Following the cloning and sequencing of the BCHE gene 7, 8),
the molecular basis,
particularly of the heterogeneous atypical and silent BCHE
phenotypes, could be unraveled. This enables DNA-based genotyping
of individual patients and populations 9-12).
The most common BCHE-mutations
are the K-variant Ala539Thr
in exon 4 with an estimate homozygote frequency of 1:100 and the
dibucain-resitant 1 variant
Asp70Gly in exon 2 with a homozygote frequency of
1:3000 in the Caucasian population. A still growing number of more
than 45 missence, nonsence, insertion, deletion and splice site
mutations in all 3 coding exons of the gene have been reported
The screening of the BCHE gene
for mutations supports the clinical diagnosis of
peudocholinesterase deficiency and enables detection of asymptomatic
carriers of mutant alleles.
peudocholinesterase deficiency, we offer a tiered analysis of the
BCHE gene: Partial sequence analysis of
exon 2 (e.g. Asp70Gly
) and exon 4 (e.g. Ala539Thr),
followed by the complete mutation screening of
exon 2 and exon 3.
When mutations are found, we
recommend analyzing the corresponding BCHE-alleles of the
patient's relatives to detect asymptomatic carrier of the gene
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