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)

The organ most frequently affected in mitochondrial disorders is the skeletal muscle (mitochondrial myopathy). Mitochondrial myopathies may be part of syndromic as well as non-syndromic mitochondrial disorders. Involvement of the skeletal muscle may remain subclinical, may manifest as isolated elevation of the creatine-kinase, or as weakness and wasting of one or several muscle groups. The course of mitochondrial myopathies is usually slowly progressive and only rarely rapidly progressive leading to restriction of mobility and requirement of a wheel chair or even muscular respiratory insufficiency. Frequently reported symptoms of mitochondrial myopathies are permanent tiredness, easy fatigability, muscle aching at rest or already after moderate exercise, muscle cramps, muscle stiffness, fasciculations and muscle weakness. The diagnosis is based on the history, clinical neurologic examination, blood chemical investigations, lactate stress test, electromyography, magnetic resonance imaging, magnetic resonance spectroscopy, muscle biopsy, biochemical investigations of the skeletal muscles, and genetic investigations. Only symptomatic therapy is available and includes physiotherapy and orthopedic supportive devices, diet, symptomatic drug therapy (analgetics, cramp-releasing drugs, antioxidants, lactate-lowering drugs, alternative energy sources, co-factors), avoidance of mitochondrion-toxic drugs, surgery (correction of ptosis or orthopedic problems), and invasive or non-invasive mechanical ventilation. General anesthesia needs to be performed in the same way as in patients with susceptibility for malignant hyperthermia.
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PMID:[Mitochondrial myopathies]. 1989 Jul 72

A patient with McArdle disease underwent bowel surgery with general anesthesia and was successfully managed. McArdle disease is a rare skeletal muscle disorder affecting approximately 1 in 100,000 people. McArdle disease, also known as type V glycogen storage disease, is an autosomal recessive inherited condition caused by a missing or nonfunctioning enzyme called myophosphorylase C. This phosphorylase is the enzyme responsible for making glucose for energy. Individuals suffering from McArdle disease have muscles that cannot properly metabolize energy and may experience fatigue and failure during strenuous activities. When a patient with McArdle disease presents for any surgical procedure, a variety of anesthesia implications should be discussed and incorporated into the overall management of his or her care. Careful attention to adequate fluid management, appropriate neuromuscular blockade choices, normothermia maintenance, normoglycemia maintenance, blood pressure monitoring, and maintaining malignant hyperthermia precautions is critical to providing safe anesthesia to this unique patient population.
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PMID:Anesthesia considerations in a patient with mcArdle disease: a case report. 2175 93

Genetical genomics has been suggested as a powerful approach to study the genotype-phenotype gap. However, the relatively low power of these experiments (usually related to the high cost) has hindered fulfillment of its promise, especially for loci (QTL) of moderate effects.One strategy with which to overcome the issue is to use a targeted approach. It has two clear advantages: (i) it reduces the problem to a simple comparison between different genotypic groups at the QTL and (ii) it is a good starting point from which to investigate downstream effects of the QTL. In this study, from 698 F2 birds used for QTL mapping, gene expression profiles of 24 birds with divergent homozygous QTL genotypes were investigated. The targeted QTL was on chromosome 1 and affected initial pH of breast muscle. The biological mechanisms controlling this trait can be similar to those affecting malignant hyperthermia or muscle fatigue in humans. The gene expression study identified 10 strong local signals that were markedly more significant compared to any genes on the rest of the genome. The differentially expressed genes all mapped to a region <1 Mb, suggesting a remarkable reduction of the QTL interval. These results, combined with analysis of downstream effect of the QTL using gene network analysis, suggest that the QTL is controlling pH by governing oxidative stress. The results were reproducible with use of as few as four microarrays on pooled samples (with lower significance level). The results demonstrate that this cost-effective approach is promising for characterization of QTL.
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PMID:An expression QTL of closely linked candidate genes affects pH of meat in chickens. 2438 78

Store-operated Ca2+ entry (SOCE) is a Ca2+ entry mechanism activated by depletion of intracellular Ca2+ stores. In skeletal muscle, SOCE is mediated by an interaction between stromal-interacting molecule-1 (STIM1), the Ca2+ sensor of the sarcoplasmic reticulum, and ORAI1, the Ca2+-release-activated-Ca2+ (CRAC) channel located in the transverse tubule membrane. This review focuses on the molecular mechanisms and physiological role of SOCE in skeletal muscle, as well as how alterations in STIM1/ORAI1-mediated SOCE contribute to muscle disease. Recent evidence indicates that SOCE plays an important role in both muscle development/growth and fatigue. The importance of SOCE in muscle is further underscored by the discovery that loss- and gain-of-function mutations in STIM1 and ORAI1 result in an eclectic array of disorders with clinical myopathy as central defining component. Despite differences in clinical phenotype, all STIM1/ORAI1 gain-of-function mutations-linked myopathies are characterized by the abnormal accumulation of intracellular membranes, known as tubular aggregates. Finally, dysfunctional STIM1/ORAI1-mediated SOCE also contributes to the pathogenesis of muscular dystrophy, malignant hyperthermia, and sarcopenia. The picture to emerge is that tight regulation of STIM1/ORAI1-dependent Ca2+ signaling is critical for optimal skeletal muscle development/function such that either aberrant increases or decreases in SOCE activity result in muscle dysfunction.
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PMID:Role of STIM1/ORAI1-mediated store-operated Ca2+ entry in skeletal muscle physiology and disease. 3041 8

Mutations in RYR1 are a common genetic cause of non-dystrophic neuromuscular disorders. To obtain baseline data concerning the prevalence of fatigue, the psychological disease burden and quality of life associated with these common conditions, we performed a questionnaire study. Seventy-two patients were included in this study, 33 with a congenital myopathy and 39 with malignant hyperthermia or exertional rhabdomyolysis. Our results showed that patients with RYR1-related myopathies have more functional impairments and significant chronic fatigue compared to healthy controls, with almost half of patients being severely fatigued. Whilst fatigue, pain and associated physical and social difficulties were more pronounced in those with permanent phenotypes, individuals with intermittent phenotypes also scored higher in all relevant categories compared to healthy controls. These findings indicate that RYR1-related myopathies, despite being often considered relatively mild conditions, are nevertheless associated with severe fatigue and functional limitations, resulting in substantial loss of quality of life. Moreover, milder but in essence similar findings in patients with RYR1-related malignant hyperthermia and rhabdomyolysis suggest that those phenotypes are not truly episodic but in fact associated with a substantial permanent disease burden. These preliminary data should help to design more comprehensive quality of life studies to inform standards of care.
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PMID:Functional impairments, fatigue and quality of life in RYR1-related myopathies: A questionnaire study. 3057 99


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