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THE relationship between hypermetabolic exertional stress injuries and malignant hyperthermia (MH) has been a topic of debate for almost 30 yr. Central to this debate is the idea that some MH susceptible (MHS) patients may develop awake nonanesthesia-related manifestations similar to that seen in porcine stress syndrome. Although a link has never been established by controlled clinical studies, individual case reports and a small number of clinical series support an association between unexpected exertional rhabdomyolysis (ER) and MH susceptibility, two syndromes characterized by abnormal intracellular skeletal muscle calcium regulation. An individual is identified as MHS if he or she has a well-documented clinical episode consistent with MH during exposure to any of the known anesthetic triggering agents, or if he or she has undergone a skeletal muscle biopsy with a positive diagnostic contracture test. However, none of the published reports of patients who presented first with ER and who were subsequently identified as MHS by a positive contracture test ever developed documented clinical MH episodes involving anesthesia. We present a case that is compelling for two reasons. First, it is the only documented case of an individual who presented first with ER, followed by a clinical MH episode during anesthesia, and then by a positive contracture test. Second, genetic analysis revealed the presence of variants in the ryanodine receptor type 1 gene (RYR1), the L-type calcium channel -1 subunit gene (CACNA1S), and the calsequestrin-1 gene (CASQ1). This report provides clinical evidence for an association between ER and MH and discusses the possible role for synergistic action among rare variants in the genes encoding proteins crucial to skeletal muscle calcium regulation.

anesthesiology

Exertional Rhabdomyolysis and Malignant Hyperthermia in a Patient with Ryanodine Receptor Type 1 Gene, L-type Calcium Channel α-1 Subunit Gene, and Calsequestrin-1 Gene Polymorphisms