malignant hyperthermia, susceptibility to, 1


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malignant hyperthermia, susceptibility to, 1

An autosomal dominant (OMIM:145600) condition of variable penetration in which a patient, when subjected to certain anaesthetics (halothane, diethyl-ether, cyclopropane, enflurane and psychotropics), develops a potentially fatal reaction (up to 70% mortality in acute episodes), which occurs in 1/15,000 administrations of anaesthesics in children and 1/50–100,000 in adults; 1/2 of cases had not been previously sensitive to anaesthesia. Anaesthetised patients may develop high fever and muscle rigidity with rhabdomyolysis, release of myoglobin, renal damage and acute renal failure. 

Clinical findings
Tachycardia, tachypnoea, cyanosis, labile blood pressure, muscle rigidity, rapid and marked hyperpyrexia, acidotic, hyperkalemic, possibly DIC, renal failure; similar reactions may be evoked in these patients by warm weather, exercise, emotional stress or without known environmental cues, and are initiated by muscular hypermetabolism due to an idiopathic increase in sarcoplasmic calcium occurring under general anaesthesia. 

Diagnosis
Muscle contraction test with halothane or caffeine challenge.
 
Management
Hypothermia, hydration, sodium bicarbonate infusion, mechanical hyperventilation, diuretics to increased urine flow, dantrolene (an agent that blocks excitation-contraction coupling between T tubules and sarcoplasmic reticulum). 

Molecular pathology
Caused by defects in RYR1, which encodes ryanodine receptor 1, a calcium channel that mediates the release of Ca2+ from the sarcoplasmic reticulum and plays a key role in triggering muscle contraction.
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