Author(s): Denborough M
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Abstract A specific inherited muscle membrane disorder predisposes to a variety of clinical problems. The most common is malignant hyperthermia (MH), a dangerous hypermetabolic state after anaesthesia with suxamethonium and/or volatile halogenated anaesthetic agents. MH may also be triggered in susceptible individuals by severe exercise in hot conditions, infections, neuroleptic drugs, and overheating in infants. Inbred pigs have provided a helpful model, and experiments on these animals and in MH-susceptible patients have shown that the essential biochemical abnormality is an increase in calcium ions in the muscle cells. This knowledge has led to a specific muscle test to identify susceptibility to MH and to a specific treatment, dantrolene; and as a result the case-fatality rate in MH has fallen from 70\% in the 1970s to 5\% today. In pigs susceptibility to MH is caused by a single mutation in the ryanodine receptor (RYR) in skeletal muscle. In man the genetics is more complex and three clinical myopathies that predispose to MH have been defined. By far the most common is inherited as a mendelian dominant characteristic and at present mutations in the human RYR account for no more than 20\% of susceptible families.
This article was published in Lancet
and referenced in Journal of Analytical & Bioanalytical Techniques