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 GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
7873 BCHE 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7873BCHE81479 81479 $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

A 25% additional charge will be applied to STAT orders. View STAT turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

Turnaround Time

18 days on average

EMAIL CONTACTS

Genetic Counselors

Geneticist

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).

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.

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).

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.

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
  • G├Ątke 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 PD, Ball EV, Mort M, Phillips AD, Shiel JA, Thomas NS, Abeysinghe S, Krawczak M, Cooper DN. 2003. Human Gene Mutation Database (HGMD): 2003 update. Human Mutation 21(6): 577-581. 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

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