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)

Chromosome 19 is short but has higher relative density of genes than other chromosomes. Increasing number of the genes coding for proteins implicated in the pathogenesis of various human diseases have been mapped on chromosome 19. Mutations of low density lipoprotein receptor (LDL-R) result in one of the most frequent mendelian inherited disorder-familial hypercholesterolemia. Mutations of insulin receptor (INSR) are causative for rare syndromes of insulin resistance and some of non insulin dependent diabetes mellitus (NIDDM). Erythropoietin receptor (EPOR) mutations are causative for rare primary familial and congenital polycythemias (PFCP). Defects of one of the largest gene in the human genome RYR 1 (ryanodine receptor gene) (> 240 kb in size) accounts for majority of malignant hyperthermia (MH) and central core disease (CCD). All these disorders represent group of receptor diseases. The amplification of GCT trinucleotide repeats in myotonic dystrophy protein kinase (DMPK) gene is causative for myotonic dystrophy (DM) and represents a new class of human gene mutations: trinucleotide repeat mutations. Apolipoprotein E (APOE) locus plays a role in pathogenesis of the late onset familial Alzheimer's disease. Translocation of EA2 gene which encodes two helix-loop-helix (HLH) transcription proteins and its fusion with PBXI or hepatic leukemia factor (HLF) leads to the leukemogenesis in subgroup of ALL. Interestingly adeno-associated virus (AAV), currently widely used as vector for gene therapy has unique capability of specific integration into human chromosome 19q.
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PMID:Human genome--chromosome no. 19. 758 75

Malignant hyperthermia (MH) is a potentially lethal disorder triggered in susceptible individuals on exposure to common anaesthetic agents. Crises reflect the consequences of disturbed skeletal muscle calcium homeostasis. MH is an autosomal dominant, genetically heterogeneous trait. Defects in a single major gene have been assumed to determine susceptibility status in individual families. However, in some pedigrees phenotypic and genotypic data are discordant. One explanation, in contrast to the current genetic model, is that susceptibility is dependent upon the effects of more than one gene. Using the transmission disequilibrium test we assessed the involvement of 8 MH candidate loci (RYR1, CACNA1S, CACNA2D1, MHS4 at 3q13.1, MHS6 at 5p, LIPE, DM1, dystrophin) by analysis of data from 130 MH nuclear families. Results suggested that variations in more than one gene may influence MH susceptibility in single families.
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PMID:Multiple interacting gene products may influence susceptibility to malignant hyperthermia. 1141 15

There is evidence for the occurrence of psychopathological symptoms in the adult form of myotonic dystrophy such as disturbance of concentration and memory, chronic depression, disturbed social behaviour, mental retardation, and hypersomnia. In this report we present a patient suffering from multisystemic myotonic myopathy without a cytosine-thymine-guanine [corrected] repeat expansion on chromosome 19q13.3 and schizophrenia. In this patient, a severe increase of creatine kinase (CK) occurred during treatment with olanzapine and amisulpride. The following risperidone medication was well tolerated without side effects. Susceptibility for malignant hyperthermia was detected by a positive in vitro contracture test. The occurrence of elevated muscle enzymes during treatment with atypical neuroleptics is suspicious as a possible side effect of neuroleptic medication and muscle disease.
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PMID:[Incompatibility of olanzapine and amisulpride in multisystemic myotonic myopathy]. 1157 7

Advances in physiology and molecular genetics have promoted greater understanding of the various clinical manifestations of muscle disorders. For example, myotonia or profound weakness may be observed in sodium channel disease (e.g., paramyotonia congenita or hyperkalemic periodic paralysis), depending on the specific channel defect or with slight changes in membrane potential. Observed effects of anesthetic techniques have been essential to elucidating the primary muscular nature of myotonia. Commonly used anesthetic medications have potentially lethal (e.g., MH) or serious (e.g., myotonic dystrophy) adverse effects. Conversely, lidocaine or propofol may have therapeutic benefit for patients with skeletal muscle sodium channel disorders. Additional investigation is required to improve our understanding of how age, gender, or other factors determine the phenotypic expression of malignant hyperthermia. Future research holds the promise for more accurate pre-anesthetic identification of persons with heritable myopathies, especially those who are asymptomatic. Enhanced awareness of multiple organ system involvement in myotonic dystrophy is essential for planning perioperative care. Patients with periodic paralysis require that we know factors that incite or inhibit the development of their attacks. Advances in bench research and detailed clinical studies will further improve our ability to provide optimal care for patients with muscle disorders.
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PMID:Malignant hyperthermia and myotonic disorders. 1229 10

Torsion of a pregnant uterus is rare, but torsion of a non-pregnant uterus is extremely rare. Abdominal pain is the major symptom. Other symptoms include vaginal bleeding, urinary tract symptoms and gastro-intestinal manifestations. We present a case of a 37-year-old white nullipara who presented at the emergency room with acute urinary retention. Medical history revealed that the patient carried the disease of myotonic dystrophy, which was diagnosed two years before. Physical examination revealed a tender, distended bladder, which was easily catheterized, draining 900 ml of clear urine. The abdomen was soft with no muscle guarding or rebound tenderness. A palpable large dense mass occupying the cul-de-sac was found during bimanual examination. Abdominal ultrasound examination revealed a large intramural leiomyoma approximately 10 cm in diameter, in the posterior wall of the uterus, which repelled the bladder. In neurological examination the muscular tone and reflexes were reduced in the lower extremities. Myotonic phenomenon was not found. The patient was thought to suffer from myotonic dystrophy and therefore the possibilities for pulmonary and cardiac complications or malignant hyperthermia had to be kept in mind during the anaesthetic management. The patient underwent an exploratory laparotomy and the uterus was found to have undergone a 60 degrees rotation along the corpus and the cervix uteri transition line. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was perfomed. The intra- and postoperative course of the patient was uneventful. In conclusion, in this patient the uterine pathology (large leiomyoma) in combination with the disease of myotonic dystrophy seemed to be the predisposing factors for the torsion of the non-pregnant uterus. Also, the anaesthetic implications for total abdominal hysterectomy in myotonic dystrophy are discussed and the international literature is reviewed.
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PMID:Torsion of a non-gravid leiomyomatous uterus in a patient with myotonic dystrophy complaining of acute urinary retention: anaesthetic management for total abdominal hysterectomy. 1285 63

We experienced an anesthetic management for a patient of myotonic dystrophy with pheochromocytoma. Much attention is required to manage myotonic dystrophy on surgical manipulation. This disease interacts with anesthetic drugs. It may cause prolongation of drug action used during anesthesia compared with the usual case. It also may cause dangerous interactions such as severe arrhythmia and malignant hyperthermia. That is why we were faced with serious limitation in choosing anesthetic and adjuvant drugs. At the same time, the case of pheochromocytoma must be handled with scrupulous care. Pheochromocytoma causes severe hypertension and sometimes tachycardia leading to intracranial hemorrhage or adrenaline-induced severe hypovolemia. Besides, laparoscopic operation was scheduled to resect the pheochromocytoma. This operation demanded the anesthetic management with artificial ventilation. It must be difficult to cope with these conditions by limited number of drugs. This time, we managed this case by epidural anesthesia with propofol and nitrous oxide without opioid and muscular relaxant. Though, this patient was not fully awake from anesthesia and could not take enough breaths on his own. We extended the period of spontaneous breathing with careful check whether the patient has resumed spontaneous breathing. It took us fourteen days till extubation.
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PMID:[Anesthetic management for a patient of myotonic dystrophy with pheochromocytoma]. 1558 84

There are many mutations in the ryanodine receptor (RyR) Ca2+ release channel that are implicated in skeletal muscle disorders and cardiac arrhythmias. More than 80 mutations in the skeletal RyR1 have been identified and linked to malignant hyperthermia, central core disease or multi-minicore disease, while more than 40 mutations in the cardiac RyR2 lead to ventricular arrhythmias and sudden cardiac death in patients with structurally normal hearts. These RyR mutations cause diverse changes in RyR activity which either excessively activate or block the channel in a manner that disrupts Ca2+ signalling in the muscle fibres. In a different myopathy, myotonic dystrophy (DM), a juvenile isoform of the skeletal RyR is preferentially expressed in adults. There are two regions of RyR1 that are variably spiced and developmentally regulated (ASI and ASII). The juvenile isoform (ASI(-)) is less active than the adult isoform (ASI(+)) and its over-expression in adults with DM may contribute to functional changes. Finally, mutations in an important regulator of the RyR, the Ca2+ binding protein calsequestrin (CSQ), have been linked to a disruption of Ca2+ homeostasis in cardiac myocytes that results in arrhythmias. We discuss evidence supporting the hypothesis that mutations in each of these situations alter protein/protein interactions within the RyR complex or between the RyR and its associated proteins. The disruption of these protein-protein interactions can lead either to excess Ca2+ release or reduced Ca2+ release and thus to abnormal Ca2+ homeostasis. Much of the evidence for disruption of protein-protein interactions has been provided by the actions of a group of novel RyR regulators, domain peptides with sequences that correspond to sequences within the RyR and which compete with the endogenous residues for their interaction sites.
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PMID:Novel regulators of RyR Ca2+ release channels: insight into molecular changes in genetically-linked myopathies. 1690 97

Malignant hyperthermia (MH) is a rare, potentially lethal, clinically and genetically heterogeneous pharmacogenic myopathy, which during or after general anesthesia manifests as MH crisis (MHC) in genetically predisposed, but otherwise mostly normal, individuals (MH susceptibles) in response to anesthetic-triggering agents. MHC can also occur in patients with central core disease. MCH-like crises have been reported in those with Duchenne/Becker muscular dystrophy, myotonic dystrophy, mitochondriopathy, and various other conditions. MH susceptibility is diagnosed if there is an MHC in the individual or family history or by the in vitro caffeine-halothane contracture test. Although screening for mutations in the ryanodine-receptor-1 gene and the dihydropyridine-receptor gene, respectively, could further substantiate the diagnosis, the caffeine-halothane-contracture test still remains the gold standard for diagnosing MH susceptibility. The most well-known triggers of an MHC are depolarizing muscle relaxants and volatile anesthetics. Therapy of an MHC comprises discontinuation of triggering agents, oxygenation, and correction of the acidosis and electrolyte disturbances, treatment of arrhythmias, cooling, and dantrolene. If MH susceptibility is not known preoperatively and an MHC unexpectedly interrupts anesthesia, consultation by a specialist in MH susceptibility after anesthesia is essential to investigate the patient for MH susceptibility or subclinical myopathy, guide laboratory investigations, manage therapy, and counsel the family on further risk. To further reduce morbidity and mortality of those with MHC, anesthesiologists and neurologists should be well educated and should strengthen their clinical vigilance. Research should be intensified and extended with regard to the development of new in vitro tests to further elucidate the heterogeneous genetic background of MH susceptibility.
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PMID:Current concepts in malignant hyperthermia. 1907 92

A 7-year-old boy with congenital myotonic dystrophy (MD) and developmental retardation underwent an emergency surgery for strangulation ileus. General anesthesia was maintained using sevoflurane and fentanyl. While intraoperative arterial blood pressure, pulse and rectal temperature remained stable, the arterial blood oxygenation gradually deteriorated during the procedure. We suspected the existence of atelectasis or some other obstructive lung lesion to be the underlying cause, and performed bronchoscopic examination which revealed a collapse of the left main bronchus. Therefore, postoperative mechanical ventilation was continued for several hours in the ICU. According to the postoperative computed tomography, the left main bronchus was sandwiched between the aortic arch and thoracic vertebra. It has been reported that MD patients have a risk of perioperative pulmonary complications, particularly in those who have severe muscular disability undergoing upper abdominal surgery. These risk factors combined with bronchial stenosis could have caused intraoperative hypoxia in our patient. We conclude that when a severe MD patient is scheduled for an upper abdominal surgery, mechanical ventilation should be considered until spontaneous recovery from muscle relaxants occurs. Also, since MD has been related to malignant hyperthermia, total intravenous anesthesia, possibly combined with regional blockade, is a preferable method of anesthesia for such patients.
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PMID:[Anesthetic management of a child with congenital myotonic dystrophy and perioperative hypoxia]. 1922 72

Myotonic dystrophy (MD) is a muscle disorder characterized by progressive muscle wasting and weakness, and is the most common form of muscular dystrophy that begins in adulthood, often after pregnancy. MD might be related to occurrence of malignant hyperthermia. Therefore, the cesarean section is often performed for the parturient with MD. We had an experience of combined spinal-epidural anesthesia for cesarean section in a parturient complicated with MD. A 40-year-old woman had rhabdomyolysis caused by ritodrine at 15-week gestation and was diagnosed as MD by electromyography. Her first baby died due to respiratory failure fourth day after birth. She had hatchet face, slight weakness of her lower extremities, and easy fatigability. Her manual muscle test was 5/5 at upper extremities and 4/5 at lower extremities. She underwent emergency cesarean section for premature rupture of the membrane, weak pain during labor, and obstructed labor at 33-week gestation. We placed an epidural catheter from T12/L1 and punctured arachnoid with 25 G spinal needle. We performed spinal anesthesia using 0.5% hyperbaric bupivacaine 1.5 ml and epidural anesthesia using 2% lidocaine 6 ml. Her anesthetic level reached bilaterally to T7 and operation started 18 minutes after combined spinal-epidural anesthesia. Her baby was born 23 minutes after the anesthesia. As her baby was 1/5 at Apgar score, the baby was tracheally intubated and artificially ventilated. The cesarean section was finished in 33 minutes uneventfully. She had no adverse events and was discharged on the 8th postoperative day. Later her baby was diagnosed as congenital MD by gene analysis. Combined spinal-epidural anesthesia with the amide-typed local anesthetic agents could be useful and safe for cesarean section in the parturient with MD.
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PMID:[Combined spinal-epidural anesthesia for cesarean section in a parturient with myotonic dystrophy]. 2071 26


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