Malignant Hyperthermia Associated with Ryanodine Receptor 1 (C7360G) Mutation in Quarter Horses

Abstract

Background: Anesthetic-induced malignant hyperthermia (MH) has been documented in Quarter Horses with a single point mutation in the ryanodine receptor 1 gene (RyR1) at nucleotide C7360G, generating a R2454G amino acid substitution. However, there have been no reports of nonanesthetic manifestations of MH in horses with the C7360G mutation.Objective: To describe clinical manifestations of Quarter Horses with the C7360G mutation. Animals: Eleven Quarter Horses with the RyR1 C7360G mutation.Methods: This prospective study included horses with suspected MH, undetermined etiology of sudden death, death within hours of onset of rhabdomyolysis, muscle rigidity, stiffness, intermittent sweating, and persistent increases in serum muscle enzyme activities. Whole blood in EDTA and skeletal muscle were processed for genetic and histochemical analysis. Medical records and pedigrees were collected when available.Results: Both anesthetic-and non-anesthetic-associated myopathic manifestations of MH occurred in halter Quarter Horses with mutation of RyR1. The disease is inherited as an autosomal dominant trait. Clinical and laboratory abnormalities were similar in both forms. Rhabdomyolysis was a common finding in both groups of horses. Skeletal muscle histochemical findings were nonspecific and compatible with a noninflammatory myopathic process.Conclusions and Clinical Importance: MH is a potentially fatal disease of Quarter Horses that could be triggered by halogenated anesthetics and other nonanesthetic factors that may include exercise, stress, breeding, illnesses, and concurrent myopathies.

Clinical Approach to Commonly Encountered Problems

“…[20][21][22][23] MH is characterized by a hypermetabolic state of muscle that generally is induced by halogenated inhalation anesthetics, depolarizing skeletal muscle relaxants, and occasionally local anesthetics or stressors such as heat or vigorous exercise. Malignant hyperthermia (MH) encompasses a group of inherited skeletal muscle disorders in which calcium metabolism is altered.…”

“…Malignant hyperthermia (MH) encompasses a group of inherited skeletal muscle disorders in which calcium metabolism is altered. 23,24 This mutation can be identified by genetic testing. [20][21][22][23] MH is characterized by a hypermetabolic state of muscle that generally is induced by halogenated inhalation anesthetics, depolarizing skeletal muscle relaxants, and occasionally local anesthetics or stressors such as heat or vigorous exercise.…”

RYR1-related rhabdomyolysis: A common but probably underdiagnosed manifestation of skeletal muscle ryanodine receptor dysfunction

“…Such a link is plausible, considering 1) an uncontrolled rise in intracellular skeletal muscle calcium as the most important shared pathomechanism [15]; and 2) the common occurrence of MH and ERM in a number of porcine [16], equine [17] and murine [18,19] [20]. Three of these patients had RYR1 mutations but only hot-spots sequencing had been performed at the time [20].…”

Tetraparesis, Hemiparesis, and Ataxia

“…Malignant hyperthermia in horses is characterized by tachypnea, progressive increase in Paco 2 even with controlled ventilation, and elevated body temperature. 979 The syndrome of malignant hyperthermia may overlap with hyperkalemic periodic paralysis and exertional rhabdomyolysis. The hyperthermic episodes can be induced by halothane anesthesia or after succinylcholine administration.…”