Scoline Apnoea: BCHE Genotyping

Diagnostic Use

Several genetic variants of human butyrylcholinesterase (EC 3.1.1.8; serum cholinesterase; pseudocholinesterase; BCHE) are reportedly associated with prolonged apnoea in patients given the muscle relaxant drug succinylcholine (Scoline). An estimation of the serum BCHE activity, dibucaine number (DN) and fluoride number (FN) have, in the past, been sufficient to identify most of the known BCHE phenotypes associated with succinylcholine sensitivity. However, several additional BCHE variants have been discovered in the last 10–20 years, which complicates the phenotyping of individuals. The molecular basis for a number of these variants has been reported, and it has become clear that multiple mutations within a single BCHE gene are not rare. BCHE phenotypes, which were previously thought to represent single mutational events, may actually result from a combination of mutations. It has, therefore, become necessary to distinguish between butyrylcholinesterase at the DNA level (BCHE) and at the protein level (BChE). The genotype of an individual represents the actual point mutations (or lack of them) present in the DNA of the BCHE gene, whilst the phenotype reflects properties of the BChE protein itself. The phenotype does not always accurately reflect the genotype. For example, inhibition tests are unable to discriminate between quantitative variants and the usual (wild-type or normal) enzyme except when in the presence of the heterozygous atypical (Dibucaine-resistant) variant. Methods employing molecular techniques more accurately reflect the genetic basis for BCHE variants.

Department

Genetics - Molecular Pathology

Delphic Registration Code

MOLP

Synonyms

butyrylcholinesterase
prolonged apnoea
succinylcholine sensitivity

Turnaround Time

4 weeks

Test Code

4301

Specimen Type

• Whole Blood

Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

3

No of Samples Required

1

Paediatric Specimen Requirements

Tube/Container Type:

Preferred

• EDTA (Lavender Cap)

Preferred Sample Volume (ml)

0.5

Additional Specimen Information

This genetic test needs nucleated cells. Please don’t centrifuge or freeze the EDTA blood tube.

If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Aliquot Instructions

Sample Type

• Whole Blood

Transport to Lab

Ambient (8 - 24 degrees Celsius)

Additional Referral/Aliquot Information

Please don’t centrifuge or freeze the EDTA blood tube.

If storing blood tube prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).

Test Method

Multiplex allele-specific PCR is used with oligonucleotides designed to detect the six BCHE gene mutations D70G (Atypical variant), V142M (“H” variant), T243M (Fluoride-1 variant), G390V (Fluoride-2 variant), E497V (“J” variant) and A539T (“K” variant) and their wild-type alleles in two separate reactions. Following PCR, the resultant products are analysed by agarose gel electrophoresis.

Non-Funded Test Cost

$120.25 (Exclusive of GST)

Billing Code

4301

Uncertainty of Measurement:
Automated bidirectional DNA sequencing has an analytical sensitivity and specificity of >99%. Note that the lower limit of variant detection of sequencing analysis is ~10%, this is important to consider in the case of mosaicism, mitochondrial, and somatic variation that is not expected to be present at 50% or 100%. This analysis will not detect variants located within intronic regions, except at the intron-exon boundaries.

Contact Information

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Contact Information

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