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

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

“…These observations support the suspected relationship between exertional heat illnesses, ERM, and MHS (Box 3) [15,25], with a fatal course especially in children illustrated in several reports. Nishio et al presented a young patient (2 years 9 months) that died of heat stroke after being left in a car in high environmental temperature.…”

“…Post mortem genetic analysis showed a novel RYR1 variant, also confirmed in his father who had a positive CHCT response and central cores on the muscle biopsy [33]. This case, and that of Capacchione [25] exemplify that (E)RM is a presentation of RYR1-related myopathies most anaesthesiologists are not familiar with [25,33]. Furthermore, most general practitioners, emergency department physicians, hospital doctors, and intensivists do not associate (E)RM with MH; thus, consideration of RYR1 mutations as a cause may be easily forgotten.…”

“…Finally, muscle biopsy showed signs of a congenital myopathy in only one patient and one carrier father; all other biopsies were normal or showed only aspecific changes. The case reported by Capacchione et al illustrates that symptoms increase in the course of several days after the strenuous exercise [25]. This was also reported by the young cyclist in Box 2: in both episodes, the myalgia manifested three to four days after the race.…”

“…Family counselling is vital to identify potentially MH-susceptible relatives [1] We performed a systematic literature review (including the patients in the studies mentioned above), based on a Pubmed search with "RYR1" and "rhabdomyolysis". This resulted in identification of several case report and small series [1,8,[21][22][23][24][25][26], and two review article [27,28] Subsequently, we also included cases from references of these articles [20,26,[29][30][31][32][33][34] and added our recent letter by Snoeck et al [35]. Finally, we added two patients from our paper on the spectrum of RYR1 related myopathies by Snoeck et al who were not included in any other publication (patients 14 and 52 [1]).…”

“…The children reported by Gener and Lavezzi also had a fatal outcome of their heat illness. [32,33] This clinical overlap has implications for some MHsusceptible patients and their capacity to exercise, as well as for clinicians treating and anesthetizing patients with histories of unexplained exertional heat and exercise illnesses [25]. [15,25,37] Exertional heat illness, ERM, and MH have similar pathophysiology: all three are hypermetabolic states that include high demand for adenosine triphosphate, accelerated oxidative, chemical, and mechanical stress of muscle, and uncontrolled increase in intracellular calcium.…”