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Pseudocholinesterase Deficiency Clinical Presentation

  • Author: Daniel R Alexander, MD; Chief Editor: Brian H Kopell, MD  more...
 
Updated: Sep 17, 2015
 

History

A personal or family history of an adverse drug reaction to one of the choline ester compounds, such as succinylcholine, mivacurium, or cocaine, may be the only clue suggesting pseudocholinesterase deficiency.

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Causes

Most clinically significant causes of pseudocholinesterase deficiency are due to one or more inherited abnormal alleles that code for the synthesis of the enzyme.

  • These abnormal alleles may result in a failure to produce normal amounts of the enzyme or in production of abnormal forms of pseudocholinesterase with altered structure and lacking full enzymatic function, as described below.
  • Patients with only partial deficiencies of inherited pseudocholinesterase enzyme activity often do not manifest clinically significant prolongation of paralysis following administration of succinylcholine unless a concomitant acquired cause of pseudocholinesterase deficiency is present. The acquired causes of pseudocholinesterase deficiency include a variety of physiologic conditions, pathologic states, and medications listed below.

Inherited causes

Inherited causes of pseudocholinesterase deficiency include the following:

The gene that codes for the pseudocholinesterase enzyme is located at the E1 locus on the long arm of chromosome 3, and 96% of the population is homozygous for the normal pseudocholinesterase genotype, which is designated as EuEu.

The remaining 4% of the population carries one or more of the following atypical gene alleles for the pseudocholinesterase gene in either a heterozygous or homozygous fashion.

Table 1. Atypical Gene Alleles for the Pseudocholinesterase Genotype (Open Table in a new window)

Ea Atypical dibucaine-resistant variant Point mutation
Ef Fluoride-resistant variant Point mutation
Es Silent variant Frameshift mutation
*These alleles may occur either in the homozygous form or in any heterozygous combination with each other, with the normal Eu allele, or with a number of additional rare variant abnormal alleles

 

In individuals with an inherited form of pseudocholinesterase deficiency, only a single atypical allele is carried in a heterozygous fashion, resulting in a partial deficiency in enzyme activity, which manifests as a slightly prolonged duration of paralysis, longer than 5 minutes but shorter than 1 hour, following administration of succinylcholine. Less than 0.1% of the general population carries 2 pseudocholinesterase gene allele mutations that will produce clinically significant effects from succinylcholine lasting longer than 1 hour.

One rare variant allele of the pseudocholinesterase gene, designated the C5 variant, actually has higher than normal enzyme activity, resulting in relative resistance to the paralytic effects of succinylcholine.

The dibucaine-resistant genetic variant form of pseudocholinesterase is identified by the percent inhibition of hydrolysis of benzyl choline caused by the addition of dibucaine to the pseudocholinesterase enzymatic assay. The dibucaine number is the percent inhibition of hydrolysis of benzyl choline by dibucaine added to the plasma sample. The normal dibucaine number for the homozygous typical genotype (EuEu) is 80%. Individuals homozygous for the atypical dibucaine resistant genotype (EaEa) have a dibucaine number of 20%, which correlates with a marked prolongation of the paralytic effect of standard doses of succinylcholine to well over 1-hour duration. Heterozygotes (EuEa) have intermediate dibucaine numbers and modest prolongation of muscle paralysis with succinylcholine. The EuEa heterozygous genotype is found in 2.5% of the general population, making it more common than all other abnormal pseudocholinesterase genotypes combined.

The fluoride-resistant pseudocholinesterase enzyme variant is identified by its percent inhibition of benzyl choline hydrolysis when fluoride is added to the assay. The fluoride number (percentage inhibition of enzyme activity in the presence of fluoride) is 60% for the EuEu genotype and is 36% for the EfEf genotype. This homozygous fluoride-resistant genotype exhibits mild to moderate prolongation of succinylcholine-induced paralysis. The heterozygous fluoride-resistant genotype usually is clinically insignificant unless accompanied by a second abnormal allele or by a coexisting acquired cause of pseudocholinesterase deficiency.

The most severe form of inherited pseudocholinesterase deficiency occurs in only 1 in 100,000 individuals who are homozygous for the silent Es genotype, with no detectible pseudocholinesterase enzyme activity. These individuals may exhibit prolonged muscle paralysis for as long as 8 hours following a single dose of succinylcholine. Gene mutations that produce silent alleles are caused by frameshift or stop codon mutations, resulting in no functional pseudocholinesterase enzyme synthesis.

Acquired causes

Acquired causes of pseudocholinesterase deficiency include the following:

Neonates, elderly individuals, and pregnant women with certain physiologic conditions may have lower plasma pseudocholinesterase activity.[4, 5]

Pathologic conditions that may lower plasma pseudocholinesterase activity include the following:

  • Chronic infections (tuberculosis)
  • Extensive burn injuries
  • Liver disease
  • Malignancy
  • Malnutrition
  • Organophosphate pesticide poisoning
  • Uremia

One study recommended estimation of the pseudocholinesterase level to classify the severity of organophosphorous poisoning and to estimate prognosis. Pseudocholinesterase levels were reduced in all the cases in this study (N = 70), with the mean level being 3,154.16 ± 2,562.40 IU/L.[10]

Iatrogenic causes

Iatrogenic causes of lower plasma pseudocholinesterase activity include plasmapheresis and medications such as the following:

  • Anticholinesterase inhibitors
  • Bambuterol
  • Chlorpromazine
  • Contraceptives
  • Cyclophosphamide
  • Echothiophate eye drops
  • Esmolol
  • Glucocorticoids
  • Hexafluorenium
  • Metoclopramide
  • Monoamine oxidase inhibitors
  • Pancuronium
  • Phenelzine
  • Tetrahydroaminacrine
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Contributor Information and Disclosures
Author

Daniel R Alexander, MD Consulting Staff, Departments of Internal Medicine and Pathology, Franklin Square Hospital Center

Daniel R Alexander, MD is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Clinical Pathology, College of American Pathologists, MedChi The Maryland State Medical Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Brian H Kopell, MD Associate Professor, Department of Neurosurgery, Icahn School of Medicine at Mount Sinai

Brian H Kopell, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of Neurological Surgeons, International Parkinson and Movement Disorder Society, Congress of Neurological Surgeons, American Society for Stereotactic and Functional Neurosurgery, North American Neuromodulation Society

Disclosure: Received consulting fee from Medtronic for consulting; Received consulting fee from St Jude Neuromodulation for consulting; Received consulting fee from MRI Interventions for consulting.

References
  1. Leadingham CL. A case of pseudocholinesterase deficiency in the PACU. J Perianesth Nurs. 2007 Aug. 22(4):265-71; quiz 272-4. [Medline].

  2. Soliday FK, Conley YP, Henker R. Pseudocholinesterase deficiency: a comprehensive review of genetic, acquired, and drug influences. AANA J. 2010 Aug. 78(4):313-20. [Medline].

  3. Maiorana A, Roach RB Jr. Heterozygous pseudocholinesterase deficiency: a case report and review of the literature. J Oral Maxillofac Surg. 2003 Jul. 61(7):845-7. [Medline].

  4. Brozović G, Mazul Sunko B, Hafner T, Bekavac I. Allergic reaction to suxamethonium during emergency caesarean section and pseudocholinesterase deficiency in the same patient. Wien Klin Wochenschr. 2014 Jul. 126 (13-14):435-8. [Medline].

  5. Zoller M, Walther S. [Residual relaxant block due to pseudocholinesterase deficiency - First manifestation in an elderly patient]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2014 Jan. 49 (1):8-11. [Medline].

  6. Lurati AR. Organophosphate exposure with pseudocholinesterase deficiency. Workplace Health Saf. 2013 Jun. 61 (6):243-5. [Medline].

  7. Araoud M, Mhenni H, Hellara I, Hellara O, Neffati F, Douki W, et al. [Plasma cholinesterase activity in hepatic diseases]. Ann Biol Clin (Paris). 2013 May-Jun. 71 (3):293-8. [Medline].

  8. Williams J, Rosenquist P, Arias L, McCall WV. Pseudocholinesterase deficiency and electroconvulsive therapy. J ECT. 2007 Sep. 23(3):198-200. [Medline].

  9. Duysen EG, Li B, Carlson M, Li YF, Wieseler S, Hinrichs SH, et al. Increased hepatotoxicity and cardiac fibrosis in cocaine-treated butyrylcholinesterase knockout mice. Basic Clin Pharmacol Toxicol. 2008 Dec. 103(6):514-21. [Medline].

  10. Chaudhary SC, Singh K, Sawlani KK, Jain N, Vaish AK, Atam V, et al. Prognostic significance of estimation of pseudocholinesterase activity and role of pralidoxime therapy in organophosphorous poisoning. Toxicol Int. 2013 Sep. 20(3):214-7. [Medline]. [Full Text].

  11. Li B, Duysen EG, Carlson M, Lockridge O. The butyrylcholinesterase knockout mouse as a model for human butyrylcholinesterase deficiency. J Pharmacol Exp Ther. 2008 Mar. 324(3):1146-54. [Medline].

  12. Cerf C, Mesguish M, Gabriel I, et al. Screening patients with prolonged neuromuscular blockade after succinylcholine and mivacurium. Anesth Analg. 2002 Feb. 94(2):461-6, table of contents. [Medline].

  13. Dietz AA, Rubinstein HM, Lubrano T. Colorimetric determination of serum cholinesterase and its genetic variants by the propionylthiocholine-dithiobis(nitrobenzoic acid)procedure. Clin Chem. 1973 Nov. 19(11):1309-13. [Medline].

  14. Jatlow P, Barash PG, Van Dyke C. Cocaine and succinylcholine sensitivity: a new caution. Anesth Analg. 1979 May-Jun. 58(3):- Van Dyke C. [Medline].

  15. Jensen FS, Viby-Mogensen J. Plasma cholinesterase and abnormal reaction to succinylcholine: twenty years' experience with the Danish Cholinesterase Research Unit. Acta Anaesthesiol Scand. 1995 Feb. 39(2):150-6. [Medline].

  16. Kalow W, Genest K. A method for the detection of atypical forms of human serum cholinesterase; determination of dibucaine numbers. Can J Biochem Physiol. 1957 Jun. 35(6):339-46. [Medline].

  17. Lange D, du Pasquier Y. [Study of cellular immunity in the course of nephro-epithelioma. Preliminary study concerning 12 cases (author's transl)]. J Urol Nephrol (Paris). 1975 Jul-Aug. 81(7-8):543-8. [Medline].

  18. Lehmann H, Liddell J, M - 196907. Human cholinesterase (pseudocholinesterase): genetic variants and their recognition. Br J Anaesth. 1969 Mar. 41(3):235-44. [Medline].

  19. Lovely MJ, Patteson SK, Beuerlein FJ, Chesney JT. Perioperative blood transfusion may conceal atypical pseudocholinesterase. Anesth Analg. 1990 Mar. 70(3):326-7. [Medline].

  20. Pantuck EJ. Plasma cholinesterase: gene and variations. Anesth Analg. 1993 Aug. 77(2):380-6. [Medline].

 
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Noninvasive ventilation. A bilevel positive airway pressure (BIPAP) prototype is shown here. Expiratory positive airway pressure is the expiratory pressure setting that determines the amount of positive end-expiratory pressure that is applied. The inspiratory positive airway pressure setting is the pressure support. The device can be used in spontaneous mode or timed mode (with a mandatory backup respiratory frequency).
Table 1. Atypical Gene Alleles for the Pseudocholinesterase Genotype
Ea Atypical dibucaine-resistant variant Point mutation
Ef Fluoride-resistant variant Point mutation
Es Silent variant Frameshift mutation
*These alleles may occur either in the homozygous form or in any heterozygous combination with each other, with the normal Eu allele, or with a number of additional rare variant abnormal alleles
Table 2. Reaction Times for Acholest Test Paper
Reaction Time Pseudocholinesterase Enzyme Activity
< 5 min Above normal
5-20 min Normal
20-30 min Borderline low
>30 min Below normal
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