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Malignant hyperthermia

Orpha number ORPHA423
Synonym(s) Hyperthermia of anesthesia
Malignant hyperpyrexia
Pharmacogenetic myopathy of anesthesia
Prevalence Unknown
Inheritance
  • Autosomal dominant
Age of onset Variable
ICD-10
  • T88.3
OMIM
UMLS
  • C0024591
MeSH
  • D008305
MedDRA
  • 10020844
SNOMED CT
  • 213026003

Summary

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely in humans, to stresses such as vigorous exercise and heat. The incidence of MH reactions ranges from 1:5,000 to 1:50,000-100,000 anesthesias. However, the prevalence of the genetic abnormalities may be as great as 1 in 3,000 individuals. MH affects humans, certain pig breeds, dogs, horses, and probably other animals. The most specific early diagnostic clue is elevation of end-expired carbon dioxide. The classic signs of MH include marked hyperthermia, tachycardia, tachypnea, increased carbon dioxide production, increased oxygen consumption, acidosis, muscle rigidity and rhabdomyolysis, all of which are related to a hypermetabolic response. In humans, the syndrome is inherited in autosomal dominant pattern. The pathophysiologic changes of MH are due to an uncontrolled rise in myoplasmic calcium, which activates biochemical processes related to muscle activation. As a result of ATP depletion, muscle membrane integrity is compromised leading to hyperkalemia and rhabdomyolysis. In most cases, the syndrome is caused by a defect in the ryanodine receptor. Over 90 mutations have been identified in the RYR-1 gene (located on chromosome 19q13.1) and at least 25 are causal for MH. Diagnostic testing relies on assessing the in vitro contracture response of biopsied muscle to halothane, caffeine, and other drugs. Elucidation of the genetic changes has led to the introduction, on a limited basis so far, of genetic testing for susceptibility to MH. As the sensitivity of genetic testing increases, molecular genetics will be increasing useful for identifying those at risk. Dantrolene sodium is a specific antagonist of the pathophysiologic changes in MH and should be available wherever general anesthesia is administered. The syndrome is likely to be fatal if untreated but thanks to the dramatic progress in understanding the clinical manifestations and pathophysiology of the syndrome, the mortality from MH has dropped from over 80% thirty years ago to less than 5% at present.

Expert reviewer(s)

  • Dr Mark DAVIS
  • Dr Danielle JAMES
  • Dr Neil POLLOCK
  • Dr Henry ROSENBERG
  • Dr Kathryn STOWELL

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Detailed information

Summary information
Emergency guidelines
  • FR (2013,pdf)
  • EN (2013,pdf)
Anesthesia guidelines
  • ES (2014,pdf)
  • EN (2014,pdf)
Review article
  • EN (2007)
Guidance for genetic testing
  • EN (2011,pdf)
Clinical genetics review
  • EN (2013)
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