Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

"Dementia" is the general term used to describe the symptom complex of intellectual deterioration in adult. Interest in accurately diagnosing dementia is a relatively recent phenomenon. This is reflected in both the development of neuroradiologic examinations, including MRI and SPECT as well as PET, and marked increase in both the incidence and prevalence of dementia associated with increase of the elderly population. The clinical evaluation remains the key to the differential diagnosis. Most cases of "typical dementia" can be diagnosed accurately by clinical criteria. However, the definitive diagnosis of "atypical dementia" still requires intensive neuroradiologic studies and histologic examination of brain to identify characteristic structural changes. In this study, we presented both neuroradiologic and neuropathologic information, which is important in diagnosing diseases that present atypical dementia syndrome. These diseases are as follows; AIDS, isolated CNS angiitis, CO intoxication. Wernicke encephalopathy, adrenoleukodystrophy, Nasu disease, CADASIL, CARASIL, glioblastoma, primary CNS lymphoma, antiphospholipid antibody syndrome, reversible posterior leukoencephalopathy syndrome, mitochondrial encephalopathy (MELAS), and subcortical vascular dementias.
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PMID:[Neuroradiologic and pathologic approaches to the diagnosis of dementia syndrome]. 1037 30

The substitution of guanine for adenine at position 3243 of the leucine tRNA gene of mitochondrial DNA was originally described in association with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). Diabetes mellitus associated with the mutation (mitochondrial diabetes) is a different phenotype from MELAS. We identified 11 patients with the mutation among 385 Japanese diabetic patients: two had MELAS and nine had mitochondrial diabetes. We present data on a male patient with mitochondrial diabetes who developed the nephrotic syndrome at the age of 23. Light microscopy revealed mesangial expansion, PAS-positive deposits and segmental sclerosis in the glomeruli. Scattered mesangial electron-dense deposits and thickening of the basement membrane were found on electron microscopy, suggesting that diabetic glomerulosclerosis accompanied by focal glomerulosclerosis (FGS). Mitochondrial diabetes may pre-dispose patients to renal complications, including forms of glomerulonephritis, such as FGS.
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PMID:Renal complications in patients with diabetes mellitus associated with an A to G mutation of mitochondrial DNA at the 3243 position of leucine tRNA. 1046 41

We report the unusual features of a female patient who had MELAS-specific A3243G mutation in mitochondrial DNA (mtDNA) and diabetes mellitus (DM). The patient showed mitochondrial myopathy, encephalopathy, lactic acidosis, and deafness but lacked the stroke-like episode. Acute hyperglycemia was noted after one attack of status epilepticus. Molecular genetic analysis demonstrated a heteroplasmic A3243G point mutation in the mtDNAs of muscle, blood cells and hair follicles. Glucagon stimulation test exhibited marked depression of pancreatic beta-cell function. However, in a further study neither this mutation, nor MELAS syndrome or DM, was found in all of her maternal relatives. A series of follow-up studies for beta-cell function also showed gradual improvement. The pedigree study led us to believe that this A3243G mutation arose from the germ line cells or occurred later in somatic tissues of the patient. We also suggest that the A3243G mutation of mtDNA may elicit the pathogenesis of a subtype of DM. Nevertheless, environmental stress may be another important factor for provocation of the disease.
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PMID:Absence of maternal A3243G mtDNA mutation and reversible hyperglycemia in a patient with MELAS syndrome. 1066 Jan 56

Mutations in human mitochondrial tRNA genes are associated with a number of multisystemic disorders. Using an assay that combines tRNA oxidation and circularization we have determined the relative amounts and states of aminoacylation of mutant and wild-type tRNAs in tissue samples from patients with MELAS syndrome (mito- chondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes) and MERRF syndrome (myoclonus epilepsy with ragged red fibers), respectively. In most, but not all, biopsies from MELAS patients carrying the A3243G substitution in the mitochondrial tRNA(Leu(UUR))gene, the mutant tRNA is under-represented among processed and/or aminoacylated tRNAs. In contrast, in biopsies from MERRF patients harboring the A8344G substitution in the tRNA(Lys)gene neither the relative abundance nor the aminoacylation of the mutated tRNA is affected. Thus, whereas the A3243G mutation may contribute to the pathogenesis of MELAS by reducing the amount of aminoacylated tRNA(Leu), the A8344G mutation does not affect tRNA(Lys)function in the same way.
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PMID:Decreased aminoacylation of mutant tRNAs in MELAS but not in MERRF patients. 1069 70

Mitochondria possess their own DNA and transcription and translation machinery for the synthesis of 13 protein subunits for the oxidative phosphorylation system, two rRNAs and 22 tRNAs. In 1988 the first human neurodegenerative diseases associated with mutations in the mitochondrial genome were described. The most recent biochemical and genetic research suggests that mitochondrial disorders are best categorized as: (i) primary mutations of the mitochondrial DNA, either sporadic or maternally inherited; (ii) nuclear mutations that result in alterations in mitochondrial DNA or intergenomic signalling defects; or (iii) Mendelian defects that affect the respiratory chain in the absence of mitochondrial DNA mutations. There is still little information about the pathophysiology of these different disorders. In order to obtain some insight into the cellular mechanisms of neurodegeneration, we examined cultured fibroblasts from patients with the MELAS (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes) syndrome, which is most frequently caused by a mutation in the mitochondrial tRNA for leucine. We found that their basal level of ionized calcium was elevated and that they could not normally sequester calcium influxes induced by depolarization. In addition, they were unable to maintain normal mitochondrial membrane potentials, as determined using a voltage-sensitive fluorescent indicator. Despite these physiological perturbations, the MELAS fibroblasts had normal concentrations of ATP. If neurons in MELAS patients have similar physiological abnormalities, their functional properties and long-term viability may be compromised.
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PMID:Mutations of the mitochondrial genome: clinical overview and possible pathophysiology of cell damage. 1098 62

MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) is one of the classic mitochondrial encephalomyopathies with variable clinical presentation and multisystem involvement. Enhanced sensitivity to neuromuscular blockade or anesthetic agents and susceptibility to malignant hyperthermia in these patients have ever been reported, all of which complicate the management of general anesthesia. To avoid these appalling troubles in general anesthesia, we chose spinal anesthesia for a patient with MELAS syndrome receiving appendectomy. The patient obtained adequate anesthesia and good recovery without neurologic sequelae. Although there is little information about the application of regional anesthesia in MELAS patients, we demonstrate that it may be a satisfactory choice. However, it is suggested that regional anesthesia is performed only when neurological abnormalities of spinal cord or peripheral nerves are definitely ruled out.
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PMID:Spinal anesthesia in MELAS syndrome: a case with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. 1100 Jun 76

We herein report a rare case of MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) and diabetes mellitus with ketoacidosis. An 18-year-old female patient was diagnosed to have diabetes mellitus and insulin therapy was thereafter initiated. At 26 years of age, she was hospitalized for diabetic ketoacidosis, soon followed by a loss of consciousness, left-sided dysmetria, and ataxic speech. MELAS was diagnosed because of the presence of ragged red fibers in a muscle biopsy. At 33 years of age, she was admitted to our hospital because of ketoacidosis and partial status epilepticus. A blood gas examination revealed as follows; arterial pH, 6.88; bicarbonate, 2.1 mmol/l; base excess - 29.8 mmol/l. The serum level of glucose had also increased to 30 mmol/l. The serum levels of lactate and B-hydroxybutyrate were elevated to 11.4 mmol/l and 1,990 micromol/l, respectively. Ketoacidosis improved by fluid replacement and continuous intravenous insulin infusion. A brain MRI demonstrated hyperintensity areas on FLAIR images in the bilateral temporal lobes and the cerebellum. A proton MRS demonstrated the abnormal lactate accumulation in the bilateral temporal and occipital lobes. Since epileptic seizures are rare in patients with diabetic ketoacidosis, such seizures may indicate the existence of MELAS syndrome.
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PMID:Ketoacidosis accompanied by epileptic seizures in a patient with diabetes mellitus and mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). 1111 21

Many different pathogenic mutations in the mitochondrial (mt) transfer RNA (tRNA) genes have been reported for patients with mitochondrial encephalomyopathy. Although some of them are recurrent, most have only been described once and appear to be restricted to one patient or to one family. The incidence of mt tRNA gene alterations is not known, even though the frequency of some recurrent mutations has been analysed both in patients and in the general population. In this study, we describe the results of stepwise screening for sequence variations in the mt tRNA genes of 166 patients selected according to several criteria. Extensive sequence analysis of the tRNA genes was performed using denaturing gradient gel electrophoresis. A total of 31 patients (19%) were found to harbour significant levels of a pathogenic mutation, thus confirming the importance of mt tRNA mutations in human pathology. Forty-three different sequence variations were found, illustrating the great diversity of the mtDNA sequence in humans. The functional assessment of all these sequence variations represented a difficult task; it was mostly based on indirect data, such as the phylogenetic conservation of modified nucleotides and the proportions of variant species in different tissues of the index case or in blood of maternal relatives. Direct demonstration of a correlation between the proportion of heteroplasmic sequence variations and the cytochrome c oxidase defect was performed at the single muscle-fibre level. Eleven heteroplasmic sequence variations were found, six of which are new mutations. One is a known Caucasian polymorphism but the other 10 are pathogenic. Two of them are the well-known pathogenic MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) (A3243G) and MERRF (myoclonic epilepsy with ragged-red fibres) (A8344G) point mutations. They were found in 23 patients. The eight other mutations were restricted to one patient. The pathogenic nature of these mutations was demonstrated directly for five of them and hypothesized from indirect arguments for the other three. Thirty-two homoplasmic sequence variations were found. Twenty-nine were considered to be polymorphisms, even though 15 of these were found for the first time in our patients and two others had been reported previously as pathogenic. The pathogenic nature of three homoplasmic variants remains questionable.
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PMID:Mitochondrial DNA transfer RNA gene sequence variations in patients with mitochondrial disorders. 1133

MELAS is characterized by mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, but cardiac involvement also frequently occurs. An 80-year-old female patient had been suffering from insulin-dependent diabetes mellitus and neurosensory hearing loss. At the age of 79 she suffered metabolic acidosis with persistent drowsiness and was subsequently found to have severe cardiac dysfunction. Muscle biopsy disclosed the presence of abnormal mitochondria, and the MELAS gene mutation (A3243G of the tRNA(Leu(UUR))) was demonstrated. It is noteworthy that this mitochondrial disease patient has survived until a great age, which shows the wide clinical spectrum of MELAS, especially in the age of onset.
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PMID:An 80-year-old mitochondrial disease patient with A3243G tRNA(Leu(UUR)) gene presenting cardiac dysfunction as the main symptom. 1139 11

A 6-year-old boy with a rare mitochondrial disease (MELAS: mitochondrial encephalopathy, lactic acidosis, stroke-like episodes) was presented to undergo adenoid resection and bilateral paracentesis. ENT surgery was performed without complications under general anaesthesia using propofol, fentanyl, and ventilation with nitrous oxide and oxygen. Routine intraoperative monitoring (ECG, noninvasive blood pressure, oxymetry and capnometry) was supplemented by frequent body temperature measurements and repeated laboratory analysis of venous blood gases, lactate, and glucose. Clinically, the postoperative course was uneventful and the boy was discharged from hospital on the first postoperative day. Signs or symptoms of malignant hyperthermia never occurred. Laboratory analysis only showed a remarkable serum lactate elevation postoperatively (6 mmol/l) which decreased on the first postoperative day (3.7 mmol/l). The present anaesthesiologic experiences with MELAS-syndrome are limited, and recommendations are mainly based on case reports. Careful preoperative physical examination with special regard to all available medical records, and anaesthetic management comparable with that in malignant hyperthermia susceptible resulted in an uneventful course in our patient. Pathogenetic aspects of mitochondrial diseases focussing on anaesthetic considerations are briefly discussed.
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PMID:[Anesthesia in mitochondrial encephalomyopathies]. 1149 20


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