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Malignant hyperthermia, susceptibility to, 3

MedGen UID:
418956
Concept ID:
C2930982
Finding
Synonyms: Malignant hyperpyrexia susceptibility type 3; Malignant hyperthermia susceptibility type 3; MHS3-Related Malignant Hyperthermia Susceptibility
 
Monarch Initiative: MONDO:0007940
OMIM®: 154276

Disease characteristics

Excerpted from the GeneReview: Malignant Hyperthermia Susceptibility
Malignant hyperthermia susceptibility (MHS) is a pharmacogenetic disorder of skeletal muscle calcium regulation associated with uncontrolled skeletal muscle hypermetabolism. Manifestations of malignant hyperthermia (MH) are precipitated by certain volatile anesthetics (i.e., halothane, isoflurane, sevoflurane, desflurane, enflurane), either alone or in conjunction with a depolarizing muscle relaxant (specifically, succinylcholine). The triggering substances cause uncontrolled release of calcium from the sarcoplasmic reticulum and may promote entry of extracellular calcium into the myoplasm, causing contracture of skeletal muscles, glycogenolysis, and increased cellular metabolism, resulting in production of heat and excess lactate. Affected individuals experience acidosis, hypercapnia, tachycardia, hyperthermia, muscle rigidity, compartment syndrome, rhabdomyolysis with subsequent increase in serum creatine kinase (CK) concentration, hyperkalemia with a risk for cardiac arrhythmia or even cardiac arrest, and myoglobinuria with a risk for renal failure. In nearly all cases, the first manifestations of MH (tachycardia and tachypnea) occur in the operating room; however, MH may also occur in the early postoperative period. There is mounting evidence that some individuals with MHS will also develop MH with exercise and/or on exposure to hot environments. Without proper and prompt treatment with dantrolene sodium, mortality is extremely high. [from GeneReviews]
Authors:
Henry Rosenberg  |  Nyamkhishig Sambuughin  |  Sheila Riazi, et. al.   view full author information

Additional description

From OMIM
Malignant hyperthermia susceptibility (MHS) is an autosomal dominant disorder of skeletal muscle which manifests as a potentially fatal hypermetabolic crisis triggered by commonly used anaesthetic agents (summary by Iles et al., 1994). For a phenotypic description and a discussion of genetic heterogeneity of malignant hyperthermia susceptibility, see MHS1 (145600).  http://www.omim.org/entry/154276

Clinical features

From HPO
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Myopathy
MedGen UID:
10135
Concept ID:
C0026848
Disease or Syndrome
A disorder of muscle unrelated to impairment of innervation or neuromuscular junction.
Exercise-induced rhabdomyolysis
MedGen UID:
867168
Concept ID:
C4021526
Finding
Rhabdomyolysis induced by exercise.
Alcohol-induced rhabdomyolysis
MedGen UID:
868941
Concept ID:
C4023355
Finding
Rhabdomyolysis induced by intake of alcohol.
Anesthetic-induced rhabdomylosis
MedGen UID:
868942
Concept ID:
C4023356
Disease or Syndrome
Rhabdomyolysis induced by anesthesia.
Viral infection-induced rhabdomyolysis
MedGen UID:
871126
Concept ID:
C4025595
Disease or Syndrome
Rhabdomyolysis induced by a viral infection.
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.
Fever
MedGen UID:
5169
Concept ID:
C0015967
Sign or Symptom
Body temperature elevated above the normal range.
Hyperkalemia
MedGen UID:
5691
Concept ID:
C0020461
Finding
An abnormally increased potassium concentration in the blood.
Hyperphosphatemia
MedGen UID:
39326
Concept ID:
C0085681
Disease or Syndrome
An abnormally increased phosphate concentration in the blood.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Malignant hyperthermia
MedGen UID:
1830388
Concept ID:
C5779784
Pathologic Function
Malignant hyperthermia is characterized by a rapid increase in temperature to 39-42 degrees C. Malignant hyperthermia may occur in response to either inhalational anesthetics such as halothane, to muscle relaxants such as succinylcholine, or to exercise.

Professional guidelines

PubMed

Haverfield EV, Esplin ED, Aguilar SJ, Hatchell KE, Ormond KE, Hanson-Kahn A, Atwal PS, Macklin-Mantia S, Hines S, Sak CW, Tucker S, Bleyl SB, Hulick PJ, Gordon OK, Velsher L, Gu JYJ, Weissman SM, Kruisselbrink T, Abel C, Kettles M, Slavotinek A, Mendelsohn BA, Green RC, Aradhya S, Nussbaum RL
BMC Med 2021 Aug 18;19(1):199. doi: 10.1186/s12916-021-01999-2. PMID: 34404389Free PMC Article
Litman RS, Smith VI, Larach MG, Mayes L, Shukry M, Theroux MC, Watt S, Wong CA
Anesth Analg 2019 Apr;128(4):652-659. doi: 10.1213/ANE.0000000000004039. PMID: 30768455
Lehmann-Horn F, Jurkat-Rott K, Rüdel R; Ulm Muscle Centre
Acta Myol 2008 Dec;27(3):98-113. PMID: 19472919Free PMC Article

Curated

Orphanet Emergency Guidelines: Malignant hyperthermia

Recent clinical studies

Etiology

Riazi S, Bersselaar LRVD, Islander G, Heytens L, Snoeck MMJ, Bjorksten A, Gillies R, Dranitsaris G, Hellblom A, Treves S, Kunst G, Voermans NC, Jungbluth H
Neuromuscul Disord 2022 Aug;32(8):628-634. Epub 2022 Jun 11 doi: 10.1016/j.nmd.2022.06.003. PMID: 35738978
Johnson T, Simmons VC, Figer Schwartz S, Tola DH
J Nurs Care Qual 2022 Jul-Sep 01;37(3):269-274. Epub 2021 Nov 17 doi: 10.1097/NCQ.0000000000000610. PMID: 34799529
Santos JM, Andrade PV, Galleni L, Vainzof M, Sobreira CFR, Schmidt B, Oliveira ASB, Amaral JLG, Silva HCA
Can J Anaesth 2017 Dec;64(12):1202-1210. Epub 2017 Sep 26 doi: 10.1007/s12630-017-0978-x. PMID: 28952030
Rosenberg H, Davis M, James D, Pollock N, Stowell K
Orphanet J Rare Dis 2007 Apr 24;2:21. doi: 10.1186/1750-1172-2-21. PMID: 17456235Free PMC Article
Rosenberg H
Hosp Pract (Off Ed) 1985 Mar 15;20(3):139, 144-5, 148 passim. doi: 10.1080/21548331.1985.11703021. PMID: 3932397

Diagnosis

Noda Y, Miyoshi H, Benucci S, Gonzalez A, Bandschapp O, Girard T, Treves S, Zorzato F
Neuromuscul Disord 2023 Dec;33(12):951-963. Epub 2023 Nov 3 doi: 10.1016/j.nmd.2023.10.019. PMID: 37996280
Johnson T, Simmons VC, Figer Schwartz S, Tola DH
J Nurs Care Qual 2022 Jul-Sep 01;37(3):269-274. Epub 2021 Nov 17 doi: 10.1097/NCQ.0000000000000610. PMID: 34799529
Rosenberg H, Davis M, James D, Pollock N, Stowell K
Orphanet J Rare Dis 2007 Apr 24;2:21. doi: 10.1186/1750-1172-2-21. PMID: 17456235Free PMC Article
Rosenberg H
Hosp Pract (Off Ed) 1985 Mar 15;20(3):139, 144-5, 148 passim. doi: 10.1080/21548331.1985.11703021. PMID: 3932397
Sunohara N, Takagi A, Nonaka I, Sugita H, Satoyoshi E
Neurology 1984 Apr;34(4):544-7. doi: 10.1212/wnl.34.4.544. PMID: 6538316

Therapy

Riazi S, Bersselaar LRVD, Islander G, Heytens L, Snoeck MMJ, Bjorksten A, Gillies R, Dranitsaris G, Hellblom A, Treves S, Kunst G, Voermans NC, Jungbluth H
Neuromuscul Disord 2022 Aug;32(8):628-634. Epub 2022 Jun 11 doi: 10.1016/j.nmd.2022.06.003. PMID: 35738978
Hogan KJ
Prog Neuropsychopharmacol Biol Psychiatry 2013 Dec 2;47:128-34. Epub 2013 Apr 3 doi: 10.1016/j.pnpbp.2013.02.018. PMID: 23562862
Reifenstahl EF, Rowshan HH
Gen Dent 2009 May-Jun;57(3):242-6; quiz 247-8. PMID: 19819813
Rosenberg H, Davis M, James D, Pollock N, Stowell K
Orphanet J Rare Dis 2007 Apr 24;2:21. doi: 10.1186/1750-1172-2-21. PMID: 17456235Free PMC Article
Rosenberg H
Hosp Pract (Off Ed) 1985 Mar 15;20(3):139, 144-5, 148 passim. doi: 10.1080/21548331.1985.11703021. PMID: 3932397

Prognosis

Guglielminotti J, Rosenberg H, Li G
BMC Anesthesiol 2020 Jan 20;20(1):19. doi: 10.1186/s12871-020-0934-0. PMID: 31959119Free PMC Article
Butala B, Brandom B
Can J Anaesth 2017 Apr;64(4):396-401. Epub 2017 Jan 6 doi: 10.1007/s12630-017-0815-2. PMID: 28063098
Riazi S, Larach MG, Hu C, Wijeysundera D, Massey C, Kraeva N
Anesth Analg 2014 Feb;118(2):381-387. doi: 10.1213/ANE.0b013e3182937d8b. PMID: 23842196
Hogan KJ
Prog Neuropsychopharmacol Biol Psychiatry 2013 Dec 2;47:128-34. Epub 2013 Apr 3 doi: 10.1016/j.pnpbp.2013.02.018. PMID: 23562862
Landau ME, Kenney K, Deuster P, Campbell W
J Clin Neuromuscul Dis 2012 Mar;13(3):122-36. doi: 10.1097/CND.0b013e31822721ca. PMID: 22538307

Clinical prediction guides

Figueroa L, Kraeva N, Manno C, Ibarra-Moreno CA, Tammineni ER, Riazi S, Rios E
Br J Anaesth 2023 Jul;131(1):47-55. Epub 2023 Feb 13 doi: 10.1016/j.bja.2023.01.008. PMID: 36792386Free PMC Article
Andrade PMV, Valim LÍM, Santos JMD, Castro I, Amaral JLGD, Silva HCAD
Braz J Anesthesiol 2023 Mar-Apr;73(2):132-137. Epub 2021 Oct 6 doi: 10.1016/j.bjane.2021.07.038. PMID: 34626754Free PMC Article
Riazi S, Bersselaar LRVD, Islander G, Heytens L, Snoeck MMJ, Bjorksten A, Gillies R, Dranitsaris G, Hellblom A, Treves S, Kunst G, Voermans NC, Jungbluth H
Neuromuscul Disord 2022 Aug;32(8):628-634. Epub 2022 Jun 11 doi: 10.1016/j.nmd.2022.06.003. PMID: 35738978
Knuiman GJ, Küsters B, Eshuis L, Snoeck M, Lammens M, Heytens L, De Ridder W, Baets J, Scalco RS, Quinlivan R, Holton J, Bodi I, Wraige E, Radunovic A, von Landenberg C, Reimann J, Kamsteeg EJ, Sewry C, Jungbluth H, Voermans NC
J Neurol 2019 Apr;266(4):876-887. Epub 2019 Feb 20 doi: 10.1007/s00415-019-09209-z. PMID: 30788618Free PMC Article
Santos JM, Andrade PV, Galleni L, Vainzof M, Sobreira CFR, Schmidt B, Oliveira ASB, Amaral JLG, Silva HCA
Can J Anaesth 2017 Dec;64(12):1202-1210. Epub 2017 Sep 26 doi: 10.1007/s12630-017-0978-x. PMID: 28952030

Recent systematic reviews

Lawal TA, Wires ES, Terry NL, Dowling JJ, Todd JJ
Orphanet J Rare Dis 2020 May 7;15(1):113. doi: 10.1186/s13023-020-01384-x. PMID: 32381029Free PMC Article

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