Malignant hyperthermia

Isaac N Pessah, Paul D. Allen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Malignant hyperthermia (MH) is a rare autosomal dominant genetic disease of calcium (Ca2+) metabolism in skeletal muscle. Its manifestations are normally silent and only made evident when susceptible patients receive general anaesthesia with volatile anaesthetic agents or succinyldicholine. Skeletal muscle hypermetabolism triggered by exposure to these agents causes a cascade of clinical events, rapidly leading to death. Early treatment with dantrolene can abort the syndrome. Muscle from MH patients is abnormally sensitive to caffeine, and this forms the basis of the halothane/caffeine contracture diagnostic test. MH susceptibility has been linked to the skeletal muscle Ca2+ release channel gene (ryanodine receptor, RYR1) on chromosome 19 and four other loci related to skeletal muscle excitation contraction coupling. Over 30 RyR1 mutations from three 'hot spot' regions have been found. Discordance between some mutations and MH susceptibility has prevented genetic testing from being generally useful for diagnosis. The effects of MH mutations on RyR1 channel physiology will be presented. The roles of other proteins including FKBP12, the slow voltage-gated channel, and calsequestrin on MH will be discussed.

Original languageEnglish (US)
Pages (from-to)277-288
Number of pages12
JournalBest Practice and Research: Clinical Anaesthesiology
Volume15
Issue number2
DOIs
StatePublished - 2001

Fingerprint

Malignant Hyperthermia
Ryanodine Receptor Calcium Release Channel
Skeletal Muscle
Caffeine
Mutation
Tacrolimus Binding Protein 1A
Calsequestrin
Dantrolene
Chromosomes, Human, Pair 19
Excitation Contraction Coupling
Inborn Genetic Diseases
Succinylcholine
Genetic Testing
Contracture
Halothane
Muscle Contraction
Routine Diagnostic Tests
General Anesthesia
Anesthetics
Calcium

Keywords

  • Ca transport
  • Hypermetabolism
  • Ryanodine receptor
  • Skeletal muscle

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Psychology(all)

Cite this

Malignant hyperthermia. / Pessah, Isaac N; Allen, Paul D.

In: Best Practice and Research: Clinical Anaesthesiology, Vol. 15, No. 2, 2001, p. 277-288.

Research output: Contribution to journalArticle

Pessah, Isaac N ; Allen, Paul D. / Malignant hyperthermia. In: Best Practice and Research: Clinical Anaesthesiology. 2001 ; Vol. 15, No. 2. pp. 277-288.
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