Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Malignant hyperthermia (MH) is a hypermetabolic disorder of skeletal muscle triggered almost exclusively by potent inhalational agents and suxamethonium. Signs of an MH reaction are non-specific and may be confused with the presentation of other problems such as sepsis and overheating of a patient. A high index of suspicion is needed to be aware of an early presentation of MH. Nine patients are presented who showed abnormal signs with an earlier anaesthetic where the possible diagnosis of an MH reaction was missed. These patients either presented later with an MH reaction, confirmed by DNA analysis and in some cases in vitro contracture testing, or were diagnosed by the identification of a causative mutation confirming MH susceptibility. The MH clinical grading scale is helpful in determining the likelihood that clinical indicators indicate a possible MH reaction. Masseter muscle rigidity is a known sign of MH, confirmed in this report by positive in vitro contracture testing and DNA analysis. Several uncommon muscle disorders have a high association with MH, and postoperative myalgia unrelated to suxamethonium can be a sign which is associated with MH. These reports emphasise the importance of a thorough family history (as the MH status was known by the family in four patients), a high index of suspicion for MH, and documentation of the possibility of MH susceptibility in the anaesthesia record.
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PMID:Evidence of malignant hyperthermia in patients administered triggering agents before malignant hyperthermia susceptibility identified: missed opportunities prior to diagnosis. 2913 81

The RYR1 gene, which encodes the sarcoplasmic reticulum calcium release channel or type 1 ryanodine receptor (RyR1) of skeletal muscle, was sequenced in 1988 and RYR1 variations that impair calcium homeostasis and increase susceptibility to malignant hyperthermia were first identified in 1991. Since then, RYR1-related myopathies (RYR1-RM) have been described as rare, histopathologically and clinically heterogeneous, and slowly progressive neuromuscular disorders. RYR1 variants can lead to dysfunctional RyR1-mediated calcium release, malignant hyperthermia susceptibility, elevated oxidative stress, deleterious post-translational modifications, and decreased RyR1 expression. RYR1-RM-affected individuals can present with delayed motor milestones, contractures, scoliosis, ophthalmoplegia, and respiratory insufficiency.Historically, RYR1-RM-affected individuals were diagnosed based on morphologic features observed in muscle biopsies including central cores, cores and rods, central nuclei, fiber type disproportion, and multi-minicores. However, these histopathologic features are not always specific to RYR1-RM and often change over time. As additional phenotypes were associated with RYR1 variations (including King-Denborough syndrome, exercise-induced rhabdomyolysis, lethal multiple pterygium syndrome, adult-onset distal myopathy, atypical periodic paralysis with or without myalgia, mild calf-predominant myopathy, and dusty core disease) the overlap among diagnostic categories is ever increasing. With the continuing emergence of new clinical subtypes along the RYR1 disease spectrum and reports of adult-onset phenotypes, nuanced nomenclatures have been reported (RYR1- [related, related congenital, congenital] myopathies). In this narrative review, we provide historical highlights of RYR1 research, accounts of the main diagnostic disease subtypes and propose RYR1-related disorders (RYR1-RD) as a unified nomenclature to describe this complex and evolving disease spectrum.
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PMID:Ryanodine receptor 1-related disorders: an historical perspective and proposal for a unified nomenclature. 3319 Jun 35


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