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)

Ornithine transcarbamylase (OTC) deficiency is an X-linked disorder of urea synthesis. Among females who carry a mutant OTC allele, there is a wide range of phenotypic variability, ranging from apparent normality to a severe onset and the resulting profound neurologic impairment observed in hemizygous males. This study was designed to define the phenotypic variability of OTC deficiency in ostensibly healthy carrier females and to compare them to noncarrier females from their own and other families. One hundred seventy-five women from 89 families participated in this study. Each completed a mailed questionnaire, allopurinol testing, and fasting plasma amino acid determinations. OTC carrier status was determined by pedigree analysis, allopurinol test results, and/or DNA mutation analysis. Overall, 79 women were identified as carriers of a mutant OTC allele (60 proband mothers, 19 relatives), and 96 women (32 proband mothers, 64 female relatives) were determined to be noncarriers. Comparison of biochemical phenotypes indicated that carriers and noncarriers do not differ in daily urinary creatinine excretion, but that carriers excrete significantly less urea nitrogen and total nitrogen, reflecting their significantly lower historically reported daily protein intake. Carriers had significantly higher levels of fasting plasma glutamine and alanine, and significantly lower levels of citrulline and arginine compared with noncarriers. Carriers and noncarriers reported similar demographic characteristics, anthropometric measurements, level of education, and medical and pregnancy histories. There was no indication of increased incidence of migraine headaches among carriers. Thus, we found no evidence that asymptomatic adult female OTC heterozygotes are at increased risk for previously unidentified health problems apart from an unknown risk for hyperammonemic encephalopathy as occurred in 3 of the carriers in this study. Because these episodes appear to be related to physiologic stress (fracture, parturition), it would seem medically prudent for carriers to be aware of this risk.
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PMID:The phenotype of ostensibly healthy women who are carriers for ornithine transcarbamylase deficiency. 985 2

Brain edema sufficient to cause intracranial hypertension and brain herniation remains a major cause of mortality in acute liver failure (ALF). Studies in experimental animal models of ALF suggest a role for ammonia in the pathogenesis of both encephalopathy and brain edema in this condition. As part of a series of studies to evaluate the therapeutic efficacy of ammonia-lowering agents, groups of rats with ALF caused by hepatic devascularization were treated with L-ornithine-L-aspartate (OA), an agent shown previously to be effective in reducing blood ammonia concentrations in both experimental and human chronic liver failure. Treatment of rats in ALF with infusions of OA (0.33 g/kg/h, intravenously) resulted in normalization of plasma ammonia concentrations and in a significant delay in onset of severe encephalopathy. More importantly, brain water content was significantly reduced in OA-treated rats with ALF. These protective effects of OA were accompanied by increased plasma concentrations of several amino acids including glutamate, gamma-aminobutyric acid (GABA), taurine, and alanine, as well as the branched-chain amino acids, leucine, isoleucine, and valine. Increased availability of glutamate following OA treatment provides the substrate for the major ammonia-removal mechanism (glutamine synthetase). Plasma (but not cerebrospinal fluid) glutamine concentrations were increased 2-fold (P <.02) in OA-treated rats, consistent with increased muscle glutamine synthesis. Direct measurement of glutamine synthetase activities revealed a 2-fold increase following OA treatment. These findings demonstrate a significant ammonia-lowering effect of OA together with a protective effect on the development of encephalopathy and brain edema in this model of ALF.
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PMID:L-ornithine-L-aspartate lowers plasma and cerebrospinal fluid ammonia and prevents brain edema in rats with acute liver failure. 1046 68

Critically ill patients are characterized by acute changes in their metabolism, which are described by the term 'hypermetabolism'. In combination with anorexia, hypermetabolism leads to a negative energy and nitrogen balance. Consequently, wound healing can be inhibited, resistance is reduced, and (multiple) organ failure can occur. With the aid of nutritional support these consequences can be counteracted. During hypermetabolism protein breakdown is increased, and it is necessary to supply extra protein in the diet of critically ill patients. The amino acid glutamine is an important source of energy for enterocytes, and extra glutamine can improve the protective function of the intestinal mucosa. Branched amino acids serve as energy source during the acute phase. Arginine can reduce symptoms of encephalopathy by improving the conversion of ammonia to urea. Extra arginine in the diet also improves resistance. Because of the increased energy demand, diets for critically ill patients should be rich in fat. Moreover, extra n-3 fatty acids can improve immune function. A diet supplemented with extra zinc seems warranted because of its beneficial effect on wound healing and its inhibitory effect on protein breakdown. The enteral route is preferred because it protects the mucosal barrier of the gut, and it is less expensive and easier than the parenteral route. An enteral diet for critically ill patients is presented. Various factors that determine the choice of technique for enteral feeding are discussed.
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PMID:[Enteral, nutritional support for critically ill patients]. 1048 74

The authors studied a 47-year-old patient who presented with an association of deafness, acute cerebral stroke-like episode, leukoencephalopathy, and extensive basal ganglia calcifications. Late onset and neuroradiologic findings were atypical for MELAS syndrome (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Strokelike episodes). A heteroplasmic G to A transition at nucleotide 4332 in the tRNA glutamine gene was identified in the patient's muscle mitochondrial DNA. The pathogenicity of the mutation was shown in single muscle fibers by the correlation between high mutation load and cytochrome c oxidase defect.
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PMID:Atypical MELAS syndrome associated with a new mitochondrial tRNA glutamine point mutation. 1117 12

Cerebral edema and hepatic encephalopathy are major complications of acute liver failure. Brain herniation caused by increased intracranial pressure as a result of cell swelling is the major cause of death in this condition. Evidence available currently suggests that the rapid accumulation of ammonia by the brain is the major cause of the central nervous system complications of acute liver failure. Increased brain ammonia may cause cell swelling via the osmotic effects of an increase in astrocytic glutamine concentrations or by inhibition of glutamate removal from brain extracellular space. Acute liver failure results in altered expression of several genes in brain, some of which code for important proteins involved in CNS function such as the glucose (GLUT-1) and glutamate (GLT-1) transporters, the astrocytic structural protein glial fibrillary acidic protein (GFAP) the "peripheral-type" benzodiazepine receptor (PTBR) and the water channel protein, aquaporin IV. Loss of expression of GLT-1 results in increased extracellular brain glutamate in acute liver failure. Experimental acute liver failure also results in post-translational modifications of the serotonin and noradrenaline transporters resulting in increased extracellular concentrations of these monoamines. Therapeutic measures currently used to prevent and treat brain edema and encephalopathy in patients with acute liver failure include mild hypothermia and the ammonia-lowering agent L-ornithine-L-aspartate.
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PMID:Alterations in expression of genes coding for key astrocytic proteins in acute liver failure. 1174 25

The anticonvulsant agent valproate (VPA) may cause hyperammonemic encephalopathy. Magnetic resonance imaging (MRI) and proton MR spectroscopic (MRS) findings in a patient with VPA-induced hyperammonemic encephalopathy are described. MRI showed a metabolic-toxic lesion pattern with bilateral T2-hyperintense lesions in the cerebellar white matter and in the globus pallidus. MR spectroscopic findings were indistinguishable from hepatic encephalopathy with severe depletion of myoinositol and choline and with glutamine excess. N-Acetylaspartate levels were moderately decreased. Quantitative MRS gave detailed insight into alterations of brain metabolism in VPA-induced encephalopathy.
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PMID:Valproate-induced encephalopathy: assessment with MR imaging and 1H MR spectroscopy. 1255 87

Acute liver failure (ALF) results in alterations of energy metabolites and of glucose-derived amino acid neurotransmitters in brain. However, the dynamics of changes in glucose metabolism remain unclear. The present study was undertaken using (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy to determine the rates of incorporation of glucose into amino acids and lactate via cell-specific pathways in relation to the severity of encephalopathy and brain edema in rats with ALF because of hepatic devascularization. Early (precoma) stages of encephalopathy were accompanied by significant 2- to 4.5-fold (P <.001) increases of total brain glutamine and lactate concentrations. More severe (coma) stages of encephalopathy and brain edema led to a further significant increase in brain lactate but no such increase in glutamine. Furthermore, (13)C isotopomer analysis showed a selective increase of de novo synthesis of lactate from [1-(13)C]glucose resulting in 2.5-fold increased fractional (13)C enrichments in lactate at coma stages. [2-(13)C]glutamine, synthesized through the astrocytic enzyme pyruvate carboxylase, increased 10-fold at precoma stages but showed no further increase at coma stages of encephalopathy. (13)C-label incorporation into [4-(13)C]glutamate, synthesized mainly through neuronal pyruvate dehydrogenase, was selectively reduced at coma stages, whereas brain GABA synthesis was unchanged at all time points. In conclusion, increased brain lactate synthesis and impaired glucose oxidative pathways rather than intracellular glutamine accumulation are the major cause of brain edema in ALF. Future NMR spectroscopic studies using stable isotopes and real-time measurements of metabolic rates could be valuable in the elucidation of the cerebral metabolic consequences of ALF in humans.
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PMID:Selective increase of brain lactate synthesis in experimental acute liver failure: results of a [H-C] nuclear magnetic resonance study. 1254 Jul 93

Valproic acid (VPA) is an effective anticonvulsant useful in many types of epilepsy and, although it is usually well tolerated, it has been associated with many neurological and systemic side effects. Among these, one of the most important is VPA-induced hyperammonemic encephalopathy (VHE): its typical signs are acute onset of impaired consciousness, focal neurologic symptoms, and increased seizure frequency. The pathogenesis of VHE is still unclear, but it has been suggested that hyperammonemia can produce encephalopathy via inhibition of glutamate uptake by astrocytes which may lead to potential neuronal injury and perhaps cerebral edema. Glutamine production is increased, whereas its release is inhibited in astrocytes exposed to ammonia. The elevated glutamine increases intracellular osmolarity, promoting an influx of water with resultant astrocytic swelling. This swelling could compromise astrocyte energy metabolism and result in cerebral edema with increased intracranial pressure. Moreover, VHE seems to be more frequently in patients with carnitine deficiency or with congenital urea cycle enzymatic defects.
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PMID:Valproate-induced hyperammonemic encephalopathy. 1260 13

We describe a rare and lethal case of arginase deficiency in a 2-day-old female infant with encephalopathy and cerebral edema. The levels of glutamine and arginine but not ammonia were markedly elevated, lending support to the "glutamine hypothesis" as the mechanism of cerebral edema in urea cycle defects.
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PMID:Arginase deficiency with lethal neonatal expression: evidence for the glutamine hypothesis of cerebral edema. 1264 Mar 89

In this report, we describe the findings of diffusion MR imaging and proton MR spectroscopy in two infants with acute necrotizing encephalopathy in which there was characteristic symmetrical involvement of the thalami. Diffusion MR images of the lesions showed that the observed apparent diffusion coefficient (ADC) decrease was more prominent in the first patient, who had more severe brain damage and a poorer clinical outcome, than in the second. Proton MR spectroscopy detected an increase in the glutamate/glutamine complex and mobile lipids in the first case but only a small increase of lactate in the second. Diffusion MR imaging and proton MR spectroscopy may provide useful information not only for diagnosis but also for estimating the severity and clinical outcome of acute necrotizing encephalopathy.
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PMID:Acute necrotizing encephalopathy: diffusion MR imaging and localized proton MR spectroscopic findings in two infants. 1267 36


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