Butyrylcholinesterase Deficiency via the BCHE Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 7873 | BCHE | 81479 | 81479,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
Turnaround Time
3 weeks on average for standard orders or 2 weeks on average for STAT orders.
Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.
Targeted Testing
For ordering sequencing of targeted known variants, go to our Targeted Variants page.
Clinical Features and Genetics
Clinical Features
Butyrylcholinesterase deficiency is an enzyme disorder characterized by prolonged apnea after the application of muscle relaxants (suxamethonium or mivacurium) to patients in connection with surgical anesthesia (Garcia et al. 2011). Butyrylcholinesterase (EC 3.1.1.8; BChE), also referred to as pseudocholinesterase, is closely related to the enzyme acetylcholinesterase (EC 3.1.1.7; AChE) and is secreted in most tissues as well as in plasma (Strelitz et al. 2014). Although the physiological function of BChE has not been fully established, this enzyme is considered to play a toxicological and pharmacological role in detoxifying or catabolizing ester-containing medications (Nogueira et al. 1990). In addition, individuals diagnosed with BChE deficiency are generally asymptomatic, except for an increased sensitivity to the muscle relaxants suxamethonium and mivacurium, which are two BChE substrates used as myorelaxants, particularly for procedures requiring for tracheal intubation (Gätke et al. 2007; Delacour et al. 2014). In patients with normal BChE levels, these muscle relaxants are rapidly hydrolyzed in plasma, often within 10 min of administration (Dimov et al. 2012). On the other hand, individuals with BChE deficiency hydrolyze these drugs at a significantly slower rate, which consequently results in a prolonged neuromuscular block that ultimately leads to apnea (Primo-Parmo et al. 1996; Yen et al. 2003). Prolonged neuromuscular block often occurs in patients with >70% BChE deficiency (Garcia et a. 2011).
Genetics
BChE deficiency is an autosomal recessive enzyme disorder that is mainly caused by pathogenic sequence variants in the BCHE gene. The BCHE gene is located on chromosome 3q26.1, consists of 3 coding exons, and spans approximately 64 kb (Allderdice et al. 1991; Gnatt et al 1990). It has been estimated that 10%-20% of the human population carries at least one variant BCHE allele (Soliday et al. 2010). The mutational spectrum of the BCHE gene includes 72 causative sequence variants, which include 61 missense/nonsense substitutions, 3 small deletions, 4 small insertions, 1 small insertion/deletion, and 1 gross insertion (Stenson et al. 2003). Most of these reported pathogenic sequence variants impart adverse effects on BChE activity by altering its catalytic function or protein expression, thus resulting in a significant decrease or absence of BChE (Maekawa et al. 1997; Delacour et al. 2014).
Clinical Sensitivity - Sequencing with CNV PG-Select
Although several acquired conditions may affect BChE activity (liver or renal diseases, malnutrition, pregnancy, malignancy), >80% of patients with BChE deficiency have pathogenic sequence variants in the BCHE gene. For example, all 17 patients presenting increased sensitivity to the muscle relaxant succinylcholine and lower BChE activity harbored causative sequence variants in the BCHE gene (Primo-Parmo et al. 1996). In another study, 52 out of 65 patients with post-succinylcholine apnea carried causative sequence variants in the BCHE gene (Yen et al. 2003).
Testing Strategy
This test provides full coverage of all coding exons of the BCHE gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
The ideal BChE test candidates have a family history of BChE deficiency as indicated by low plasma levels and/or enzyme activity. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in BCHE.
The ideal BChE test candidates have a family history of BChE deficiency as indicated by low plasma levels and/or enzyme activity. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in BCHE.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| BCHE | 177400 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Butyrylcholinesterase Deficiency | 177400 |
Citations
- Allderdice PW, Gardner HA, Galutira D, Lockridge O, LaDu BN, McAlpine PJ. 1991. The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26. Genomics 11(2): 452-454. PubMed ID: 1769657
- Delacour H, Lushchekina S, Mabboux I, Bousquet A, Ceppa F, Schopfer LM, Lockridge O, Masson P. 2014. Characterization of a novel BCHE "silent" allele: point mutation (p.Val204Asp) causes loss of activity and prolonged apnea with suxamethonium. PLoS One 9(7): e101552. PubMed ID: 25054547
- Dimov D, Kanev K, Dimova I. 2012. Correlation between butyrylcholinesterase variants and sensitivity to soman toxicity. Acta Biochimica Polonica 59(2): 313-316. PubMed ID: 22696303
- Garcia DF, Oliveira TG, Molfetta GA, Garcia LV, Ferreira CA, Marques AA, Silva WA Jr. 2011. Biochemical and genetic analysis of butyrylcholinesterase (BChE) in a family, due to prolonged neuromuscular blockade after the use of succinylcholine. Genetics and Molecular Biology 34(1): 40-44. PubMed ID: 21637541
- Gätke MR, Bundgaard JR, Viby-Mogensen J. 2007. Two novel mutations in the BCHE gene in patients with prolonged duration of action of mivacurium or succinylcholine during anaesthesia. Pharmacogenetics and Genomics 17(11): 995-999. PubMed ID: 18075469
- Gnatt A, Prody CA, Zamir R, Lieman-Hurwitz J, Zakut H, Soreq H. 1990. Expression of alternatively terminated unusual human butyrylcholinesterase messenger RNA transcripts, mapping to chromosome 3q26-ter, in nervous system tumors. Cancer Research 50(7): 1983-1987. PubMed ID: 2317787
- Maekawa M, Sudo K, Dey DC, Ishikawa J, Izumi M, Kotani K, Kanno T. 1997. Genetic mutations of butyrylcholine esterase identified from phenotypic abnormalities in Japan. Clinical Chemistry 43(6 Pt 1): 924-929. PubMed ID: 9191541
- Nogueira CP, McGuire MC, Graeser C, Bartels CF, Arpagaus M, Van der Spek AF, Lightstone H, Lockridge O, La Du BN. 1990. Identification of a frameshift mutation responsible for the silent phenotype of human serum cholinesterase, Gly 117 (GGT----GGAG). American Journal of Human Genetics 46(5): 934-942. PubMed ID: 2339692
- Primo-Parmo SL, Bartels CF, Wiersema B, van der Spek AF, Innis JW, La Du BN. 1996. Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE) gene. American Journal of Human Genetics 58(1): 52-64.
PubMed ID: 8554068 - Primo-Parmo SL, Bartels CF, Wiersema B, van der Spek AF, Innis JW, La Du BN.1996. Characterization of 12 silent alleles of the human butyrylcholinesterase (BCHE) gene. American Journal of Human Genetics 58(1): 52-64.
- Soliday FK, Conley YP, Henker R. 2000. Pseudocholinesterase deficiency: a comprehensive review of genetic, acquired, and drug influences. American Association of Nurse Anesthesists Journal 78(4): 313-320. PubMed ID: 20879632
- Stenson et al. 2003. PubMed ID: 12754702
- Strelitz J, Engel LS, Keifer MC2. 2014. Blood acetylcholinesterase and butyrylcholinesterase as biomarkers of cholinesterase depression among pesticide handlers. Occupational and Environmental Medicine 71(12): 842-847. PubMed ID: 25189163
- Yen T, Nightingale BN, Burns JC, Sullivan DR, Stewart PM. 2003. Butyrylcholinesterase (BCHE) genotyping for post-succinylcholine apnea in an Australian population. Clinical Chemistry 49(8): 1297-1308. PubMed ID: 12881446
Ordering/Specimens
Ordering Options
We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.
myPrevent - Online Ordering
- The test can be added to your online orders in the Summary and Pricing section.
- Once the test has been added log in to myPrevent to fill out an online requisition form.
- PGnome sequencing panels can be ordered via the myPrevent portal only at this time.
Requisition Form
- A completed requisition form must accompany all specimens.
- Billing information along with specimen and shipping instructions are within the requisition form.
- All testing must be ordered by a qualified healthcare provider.
For Requisition Forms, visit our Forms page
If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.
Specimen Types
Specimen Requirements and Shipping Details
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