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)

Multi-minicore Disease (MmD) is a recessively inherited neuromuscular disorder characterized by multiple cores on muscle biopsy and clinical features of a congenital myopathy. Prevalence is unknown. Marked clinical variability corresponds to genetic heterogeneity: the most instantly recognizable classic phenotype characterized by spinal rigidity, early scoliosis and respiratory impairment is due to recessive mutations in the selenoprotein N (SEPN1) gene, whereas recessive mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been associated with a wider range of clinical features comprising external ophthalmoplegia, distal weakness and wasting or predominant hip girdle involvement resembling central core disease (CCD). In the latter forms, there may also be a histopathologic continuum with CCD due to dominant RYR1 mutations, reflecting the common genetic background. Pathogenetic mechanisms of RYR1-related MmD are currently not well understood, but likely to involve altered excitability and/or changes in calcium homeoestasis; calcium-binding motifs within the selenoprotein N protein also suggest a possible role in calcium handling. The diagnosis of MmD is based on the presence of suggestive clinical features and multiple cores on muscle biopsy; muscle MRI may aid genetic testing as patterns of selective muscle involvement are distinct depending on the genetic background. Mutational analysis of the RYR1 or the SEPN1 gene may provide genetic confirmation of the diagnosis. Management is mainly supportive and has to address the risk of marked respiratory impairment in SEPN1-related MmD and the possibility of malignant hyperthermia susceptibility in RYR1-related forms. In the majority of patients, weakness is static or only slowly progressive, with the degree of respiratory impairment being the most important prognostic factor.
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PMID:Multi-minicore Disease. 1763 Oct 35

A 10-month-old boy presented with gross motor delay and muscle weakness, especially in both lower limbs. At age 5, he developed lordosis, talipes, and planovalgus. His grandmother died of malignant hyperthermia during surgery. On neurological examination, he had mild proximal muscle weakness and atrophy, decreased deep tendon reflexes and Gowers' sign, but his intelligence was normal. The electromyogram showed myopathic pattern. Muscle biopsy revealed type 1 fiber atrophy and central core abnormalities. We report this case of central core disease with a family history of malignant hyperthermia during surgery.
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PMID:Central core disease with family history of malignant hyperthermia: report of one case. 1826 44

Muscle disorders are a common cause of disability in horses. For many years, clinical manifestations such as muscle pain, exercise intolerance, weakness, and stiffness were believed to be caused by a single syndrome. However, in the past years a broad spectrum of muscle disorders have been recognized including glycogen and polysaccharide storage myopathies, malignant hyperthermia, mitochondrial myopathy, hyperkalemic periodic paralysis and others. For some, a specific mutation has been identified. Recognition of the myopathic clinical phenotype and thorough clinical, electrodiagnostic, and histological evaluations are essential to further our understanding of equine myopathies. Advances in understanding equine myopathies may potentially benefit other species including humans.
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PMID:A review of equine muscle disorders. 1839 47

Hemiplegic migraine (HM) is a rare variety of migraine with aura characterized by the presence of a motor weakness during the aura. Hemiplegic migraine has two main forms according to the familial history: patients with at least one first- or second-degree relative who has aura including motor weakness have familial hemiplegic migraine (FHM); patients without such familial history have sporadic hemiplegic migraine (SHM). The prevalence of HM is one in 10,000 with FHM and SHM being equally frequent. Typical HM attacks include a motor weakness that is always associated with other aura symptoms, the most frequent being sensory, visual and speech disorders. In addition, basilar-type symptoms occur in up to 70% of the patients. Severe attacks may occur in FHM as well as in SHM with prolonged hemiplegia, confusion, coma, fever and seizures. The clinical spectrum also includes permanent cerebellar signs (nystagmus, ataxia, dysarthria) and less frequently various types of seizures and intellectual deficiency. FHM is the only variety of the autosomal dominant migraine and all three know genes encode ion-transporters. A genetic diagnosis is now possible by screening the three known genes involved in FHM (CACNA1A, ATP1A2 and SCNA1). Prognosis is usually good. Treatment is similar to approaches used in other varieties of migraine with aura, excepted for triptans that are contraindicated in MHF/MHS. Based on new pathophysiological insight, preventive treatments by various antiepileptic agents seem promising.
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PMID:[Familial and sporadic hemiplegic migraine]. 1840 71

We describe the anaesthetic management of a 21-year-old lady with central core disease for elective Caesarean section. Central core disease is characterised by muscle weakness, skeletal deformities and susceptibility to malignant hyperthermia. Total intravenous anaesthesia was used because of the combination of potential malignant hyperthermia, severe kyphoscoliosis and extensive spinal scarring. The authors believe there is no previous report of propofol and remifentanil being used in these circumstances. A short review of central core disease and its anaesthetic implications is provided.
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PMID:Caesarean section in a complicated case of central core disease. 1841 56

Malignant hyperthermia is a rare, potentially life threatening pharmacogenetic disorder triggered by volatile anaesthetics and depolarizing muscle relaxants. The clinical picture comprises rhabdomyolysis, metabolic and respiratory acidosis, and hyperthermia. Carnitine palmitoyltransferase II deficiency is a metabolic myopathy affecting the transport of fatty acids into the mitochondria, leading to impaired energy supply under stressful conditions resulting in muscle weakness and rhabdomyolysis. It was postulated in a previous study that some patients with the MH phenotype have a carnitine palmitoyltransferase deficiency. To investigate a potential association, we tested 18 individuals with proven MH susceptibility for impairment of carnitine palmitoyltransferase enzyme activity in muscle. Enzyme activity was normal in all individuals tested indicating no impairment of the CPT system in this sample of malignant hyperthermia susceptible individuals. Thus our data do not support the hypothesis that susceptibility to malignant hyperthermia has an effect on the carnitine palmitoyltransferase enzyme system.
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PMID:No carnitine palmitoyltransferase deficiency in skeletal muscle in 18 malignant hyperthermia susceptible individuals. 1843 May 72

Native American myopathy (NAM) [OMIM 255995], a putative autosomal recessive disorder, was first reported in the Lumbee Indians of North Carolina. NAM features include congenital weakness and arthrogryposis, cleft palate, ptosis, short stature, kyphoscoliosis, talipes deformities, and susceptibility to malignant hyperthermia (MH) provoked by anesthesia. This report documents the phenotypic complexity and natural history of this rare congenital disorder in fourteen individuals with NAM. Findings include a previously unreported 36% mortality by age 18. Based on this study, our conservative estimate for prevalence of NAM within the Lumbee population is approximately 2:10,000; however, birth incidence remains unknown.
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PMID:Native American myopathy: congenital myopathy with cleft palate, skeletal anomalies, and susceptibility to malignant hyperthermia. 1855 14

Mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been associated with a wide range of phenotypes including the malignant hyperthermia (MH) susceptibility trait, Central Core Disease (CCD) and other congenital myopathies characterized by early onset and predominant proximal weakness. We report a patient presenting at 77 years with a predominant axial myopathy associated with prominent involvement of spine extensors, confirmed on MRI and muscle biopsy, compatible with a core myopathy. RYR1 mutational analysis revealed a novel heterozygous missense mutation (c.119G>T; p.Gly40Val) affecting the RYR1 N-terminus, previously predominantly associated with MH susceptibility. This case expands the spectrum of RYR1-related phenotypes and suggests that MH-related RYR1 mutations may give rise to overt neuromuscular symptoms later in life, with clinical features not typically found in CCD due to C-terminal hotspot mutations. Late-onset congenital myopathies may be under-recognised and diagnosis requires a high degree of clinical suspicion.
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PMID:Late-onset axial myopathy with cores due to a novel heterozygous dominant mutation in the skeletal muscle ryanodine receptor (RYR1) gene. 1930 94

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

Rhabdomyolysis, a term used to describe the rapid breakdown of striated muscle, is characterized by rupture and necrosis of muscle fibers. This process results in the release of cell breakdown products into the bloodstream and extracellular space. Although direct muscle injury remains the most common cause of muscle injury, additional causes include hereditary enzyme disorders, drugs, toxins, endocrinopathies, malignant hyperthermia, neuroleptic malignant syndrome, heatstroke, hypothermia, electrolyte alterations, diabetic ketoacidosis and non-ketotic hyperosmolar coma, severe hypo- or hyperthyroidism and bacterial or viral infections. The classic triad of symptoms includes muscle pain, weakness and dark urine, although more than 50% of the patients do not complain of muscle pain or weakness. Additional systemic symptoms include fever, general malaise, tachycardia, nausea and vomiting. The laboratory diagnosis is based essentially on the measurement of creatine kinase in serum or plasma. Plasma and urine myoglobin measurement might be useful in the early stages of the syndrome and for identifying a subset of patients with minor skeletal muscle injury. Patient monitoring is pivotal (the mortality rate is as high as 8%), and should be focused on preventing the detrimental consequences, that often include renal disease and coagulopathy. In the pre-hospital setting, forced hydration with 1.5-2 L of sterile saline solution should be started immediately, followed by 1.5-2 L/h. Following hospital admission, continuous hydration should be ensured, alternating the saline solution with a 5% glucose solution. In the presence of myoglobinuria, urine should be alkalinized by use of sodium bicarbonate solution. Clin Chem Lab Med 2010;48:749-56.
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PMID:Rhabdomyolysis: historical background, clinical, diagnostic and therapeutic features. 2044 60


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