Malignant Hyperthermia Susceptibility and Related Diseases

MALIGNANT hyperthermia (MH) is an inherited disorder of skeletal muscle that manifests clinically as a hypermetabolic crisis when a susceptible individual receives a halogenated inhalational anesthetic agent or succinylcholine.1 –3 The clinical signs that ensue from this exposure in susceptible individuals include hypercapnia, masseter muscle and/or generalized muscle rigidity, acidosis, peaked T waves that indicate hyperkalemia, and hyperthermia and are caused by the dysregulated entry of myoplasmic calcium, which results in a hypermetabolic cascade involving sustained muscular contractures, depletion of adenosine triphosphate, and muscle cell death.4 The inheritance of pathogenic variants (i.e., mutations) in three genes are primarily associated with MH susceptibility and account for the genetic basis of approximately 70% of patients investigated (fig. 1). The majority of MH –associated variants are found within theRYR1 gene that encodes the skeletal muscle ryanodine receptor type I protein.2,5 –7 This protein regulates the movement of calcium from the sarcoplasmic reticulum into the intracellular space of the muscle cell. In MH –susceptible individuals, abnormalities of the ryanodine receptor result in the accumulation of excessive myoplasmic calcium in the presence of one of the anesthetic triggering agents. Nearly 700 variants have been identified inRYR1; however, only 35 have been functionally validated as MH –causative pathogenic variants (an up-to-date list ...

Source: Anesthesiology - December 12, 2017 Category: Anesthesiology Source Type: research