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)

In malignant hyperthermia, myophosphorylase reaction shows characteristic changes that take place within minutes: (1) a generally strongly weakened reaction; (2) numerous negatively reacting fibres; (3) frequently, fibre sections that show spotty and/or striatal weak or negative reactions and fibre sections with strong striatal reactions with relatively narrow sarcomere spacings (a "sign of hypercontraction"). Obviously, the morphological findings that show characteristic "striated fibres" are typical of the malignant hyperthermia syndrome! It is important to note that the muscular fibres showing such changes are, as a rule, inconspicuous when using other stains and reactions. These pathological myophosphorylase reactions were observed in five deceased patients (one independently of anaesthesia after an extended walk) and in 19 pigs (18 times after halothane testing and once in an experimental animal with clinical evidence of the presence of malignant hyperthermia). These reactions were not noted in pigs with negative halothane reactivity or prior to halothane testing. They were also not seen in a large number of very different healthy and diseased control and reference cases from our biopsy and autopsy material. Myophosphorylase reaction enables convincing demonstration of malignant hyperthermia, past or present. Hence, it is possible to elucidate puzzling deaths or verify apparently clear death occurring during or subsequent to anaesthesia or simply following stress ("human stress syndrome"). Many of these deaths doubtlessly escape the attention of clinicians using the usual morphological examination methods. However, the reaction cannot be used to identify potential victims.
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PMID:[Pathological myophosphorylase reaction in malignant hyperthermia]. 405 Jan 36

The ratio of muscle phosphorylase a to total phosphorylase, expressed as a percent, was determined in vastus lateralis muscle of 26 patients to examine the efficacy of this parameter as a method for screening for susceptibility to malignant hyperthermia (MH). As standard screening, all patients also had muscle contracture responses determined to 2% halothane and 0.25-32 mM caffeine at 37 degrees C. Each drug was given separately and not combined. Nine patients were susceptible to MH, based upon caffeine threshold of 2 mM or less (seven patients) or a rapidly developing contracture tension to halothane of more than 400 mg (seven patients, including five with positive caffeine responses). Mean phosphorylase ratio in these nine patients was 14.5 +/- 2.0% (mean, SEM). In the 17 nonsusceptible patients mean phosphorylase ratio (12.4 +/- 1.9%) was not significantly different. The range of phosphorylase ratios in susceptible patients was 6.5-26% while 13 nonsusceptible patients had ratios greater than 6% and up to 29%. The unacceptably high number of false-positive responses in nonsusceptible patients precludes the use of phosphorylase ratio as a definitive diagnostic test.
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PMID:Phosphorylase ratio and susceptibility to malignant hyperthermia. 629 36

We report on 31 patients and 3 affected siblings (17 males and 17 females) from Southern France with McArdle disease (two from Spanish and three from Portuguese background). Molecular analysis revealed the presence of five previously described mutations: the common p.R50X nonsense mutation, the p.R94W and p.V456M missense mutations, the p.K609K conservative mutation which generates an aberrant splicing, and the p.K754fs frameshift mutation; and 10 new molecular defects: eight missense mutations at homozygous (p.G136D) or heterozygous state (p.T379M, p.G449R, p.T488I, p.R490Q, p.R570Q, p.R590H, and p.R715W), one nonsense mutation p.R650X and one deletion (p.delK170). Our results confirm that the p.R50X nonsense mutation is also the most common associated with myophosphorylase deficiency in the Southern French population: 21 of 25 French unrelated patients (15 homozygous and six heterozygous, i.e., 72% of the mutated alleles). Two patients, one from Algeria and one from Tunisia, were homozygous for a previously identified missense mutation p.V456M in a Moroccan subject. Our findings further demonstrate molecular heterogeneity of myophosphorylase deficiency, absence of genotype-phenotype correlation and expand the already crowded map of mutations within the myophosphorylase gene. Our study also provides evidence for increased medical interest of malignant hyperthermia susceptibility (MHS) because of 34 McArdle disease patients, three and two affected siblings were contracture-tested and found to be positive.
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PMID:Molecular characterization of myophosphorylase deficiency (McArdle disease) in 34 patients from Southern France: identification of 10 new mutations. Absence of genotype-phenotype correlation. 1732 73

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

McArdle disease, known as type V glycogen storage disease, is a rare skeletal muscle disorder. Patients with McArdle disease lack skeletal muscle specific glycogen phosphorylase, and myophosphorylase. This subsequently leads to an elevation in serum creatine kinase levels, and results in suffering from exercise intolerance. They have such anesthesiological problems as follows; rhabdomyolysis, myoglobinuria, acute renal failure, and a higher risk of developing malignant hyperthermia. We report a case of general anesthesia for a patient with McArdle disease. The patient was a 38-year-old woman who underwent dilation and curettage. Anesthesia was induced by intravenous administrations of fentanyl and propofol. For maintenance of anesthesia, we used total intravenous anesthesia with propofol. We avoided the use of neuromuscular blockades throughout the operation. There were no signs of rhabdomyolysis, myoglobinuria, worsening muscle weakness, or occurrence of malignant hyperthermia in the perioperative period, and the patient recovered uneventfully.
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PMID:[Anesthesia in a Patient with McArdle Disease]. 2668 76