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 deficiency is an X linked disorder and the most common inherited cause of hyperammonaemia. Fluctuating concentrations of ammonia, glutamine, and other excitotoxic amino acids result in a chronic or episodically recurring encephalopathy. A heterozygous female patient first presented with protein intolerance, attacks of vomiting, and signs of mental retardation in early childhood. At the age of 16 complex partial seizures occurred which were treated with sodium valproate. Seven days after initiation of valproate therapy, she developed severe hyperammonaemic encephalopathy with deep somnolence. The maximum concentration of ammonia was 480 micromol/l. After withdrawal of valproate, three cycles of plasma dialysis, and initiation of a specific therapy for the inborn metabolic disease, ammonia concentrations fell to normal values. The patient remitted, returning to her premorbid state. Valproate can cause high concentrations of ammonia in serum in patients with normal urea cycle enzymes and may worsen a pre-existing hyperammonaemia caused by an enzymatic defect of the urea cycle. Sufficient diagnostic tests for the detection of metabolic disorders must be performed before prescribing valproate for patients with a history of encephalopathy.
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PMID:Hyperammonaemic encephalopathy after initiation of valproate therapy in unrecognised ornithine transcarbamylase deficiency. 959 92

Recent advances in the diagnosis and treatment of inborn errors of metabolism have improved substantially the prognosis for many of these conditions. This makes it essential that the practicing pediatrician be familiar with the clinical presentation of these disorders. A practical clinical approach to the recognition of inborn errors of metabolism in the young infant is presented in this review. Indications for specific laboratory studies are discussed. Guidelines are provided for the stabilization and emergency treatment of critically ill infants. This approach will identify those infants who will benefit from additional evaluation and specific treatment. Many of the inborn errors of metabolism, including urea cycle defects, organic acidemias, and certain disorders of amino acid metabolism, present in the young infant with symptoms of an acute or chronic metabolic encephalopathy. Typical symptoms include lethargy, poor feeding, apnea or tachypnea, and recurrent vomiting. Metabolic acidosis and/or hyperammonemia are observed in many of these conditions, but there are notable exceptions, including nonketotic hyperglycinemia and molybdenum co-factor deficiency. Therefore, appropriate laboratory testing for metabolic disorders should be performed in any infant who exhibits these findings. Although sepsis may be the initial consideration in a neonate with these symptoms, inborn errors of metabolism should always be in the differential diagnosis, particularly in a full-term infant with no specific risk factors. Hypoglycemia may be the predominant finding in a number of inborn errors of metabolism, including glycogen storage disorders, defects in gluconeogenesis, and fatty acid oxidation defects. The latter disorders, among the most common encountered, exhibit marked clinical variability and also may present as a sudden death, a Reye's-like episode, or a cardiomyopathy. Jaundice or other evidence of hepatic dysfunction is the mode of presentation of another important group of inborn errors of metabolism including galactosemia, hereditary tyrosinemia, neonatal hemochromatosis, and a number of other conditions. A subset of lysosomal storage disorders may present very early with coarse facial features, organomegaly, or even hydrops fetalis. Specific patterns of dysmorphic features and congenital anomalies characterize yet another group of inherited metabolic disorders, such as Zellweger syndrome and the Smith-Lemli-Opitz syndrome. Each of these symptom complexes, and the appropriate evaluation of the affected infants, is discussed in more detail in this review.
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PMID:Inborn errors of metabolism in infancy: a guide to diagnosis. 983 97

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

A 6 year old boy developed hyperammonaemic encephalopathy following a subureteric injection for treatment of vesicoureteric reflux. The hyperammonaemia may be explained by a postoperative urinary tract infection with a urea splitting organism, leading to raised urine ammonia that was absorbed easily across a dilated urinary tract. Agitation and alteration in consciousness level following a urological procedure, in a child with a dilated urinary tract, may be signs of a treatable hyperammonaemic encephalopathy.
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PMID:Hyperammonaemic encephalopathy after a subureteric injection for vesicoureteric reflux. 987 52

Six enzyme defects of the urea cycle have been described. Ornithine transcarbamylase deficiency is the most frequent of these diseases. The cumulative frequency is 1:8000. Most patients become symptomatic in childhood, but onset of symptoms may occur later in childhood or even adulthood. The patients present with recurrent episodes of an unspecific acute encephalopathy, seizures and clouding of consciousness to a variable degree. Focal neurological signs such as hemiparesis, aphasia or ataxia may also occur. These episodes may be triggered by infection, protein overload or drugs. Diagnostic are increased blood ammonia levels. Characteristic patterns of plasma amino acids and the determination of orotic acid in the urine mostly discriminate the individual disorders. Further diagnostic steps include the allopurinol challenge test, liver or skin biopsy for measurement of enzyme activity and molecular genetic studies. Treatment requires restriction of protein intake, supplementation of arginine and activation of alternative pathways of nitrogen excretion with benzoate or phenylbutyrate. Untreated, the acute episode may be lethal. Long-term treatment improves the clinical outcome considerably. Urea cycle defects should be included in the differential diagnosis of any encephalopathy or coma of unclear origin, and blood ammonia should be determined early in the evaluation of such patients.
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PMID:[Enzyme defects of the urea cycle in differential acute encephalopathy diagnosis in adulthood. Diagnosis and current therapy concepts]. 1009 45

Upper gastrointestinal bleeding causes increased urea concentrations in patients with normal liver function and high ammonia concentrations in patients with impaired liver function. This ammoniagenesis may precipitate encephalopathy. The haemoglobin molecule is unique because it lacks the essential amino acid isoleucine and has high amounts of leucine and valine. Upper gastrointestinal bleeding therefore presents the gut with protein of very low biologic value, which may be the stimulus to induce a cascade of events culminating in net catabolism. This may influence the function of rapidly dividing cells and short half-life proteins. We hypothesize that, following a variceal bleed in a cirrhotic patient, the lack of isoleucine in blood protein is the cause of the exaggerated ammoniagenesis and catabolism. We propose that intravenous administration of isoleucine may serve as a simple therapeutic that transforms blood protein in a balanced protein, resulting in only a short-lived rise in ammonia and urea production, and preventing interference with protein synthesis.
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PMID:Upper gastrointestinal bleeding: an ammoniagenic and catabolic event due to the total absence of isoleucine in the haemoglobin molecule. 1045 31

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

Partially nephrectomized (NX) and sham-operated mice were biochemically and behaviourally compared, 10 days, 1 month and 1 year post-surgery. Plasma urea and creatinine concentrations were mildly increased in all NX groups, but creatinine clearance was significantly decreased, 10 days post-surgery only. NX mice showed lower body weights and reduced growth. Wire suspension and rotarod indicated unaffected motor functions, but NX mice did show reduced ambulation and swimming velocity, 10 days post-surgery. Hidden-platform water maze indicated a spatial learning impairment in NX mice, 10 days post-surgery, which could not be entirely reduced to motor incapacity. The acute behavioural deficits in these mildly uremic mice may relate to analogous symptoms in uraemic encephalopathy, a poorly understood brain syndrome occurring in uraemic patients.
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PMID:Behavioural deficits during the acute phase of mild renal failure in mice. 1064 93

The clinical consequences of acute liver failure are associated with high mortality. Intensive medical intervention is required to treat the symptoms of liver failure, including coagulopathy, metabolic instability, and encephalopathy. Providing temporary liver support with an extracorporeal liver assist device could stabilize the patient until a donor liver became available or the patient's own liver was able to recover. The use of human hepatocytes as the biologic component of the assist device is precluded by the scarcity of available tissue and the limited proliferative potential of adult hepatocytes in vitro. Consequently, porcine hepatocytes are being evaluated as a cell source for liver assist devices. Maintaining differentiated function in isolated hepatocytes, however, remains a challenge in the development of this technology and is complicated by the fact that the key therapeutic functions for short-term survival have not been well defined. Several approaches have been effective in prolonging rodent hepatocyte function in vitro, including manipulation of extracellular matrix. Here, we have investigated porcine hepatocyte function in vitro with a specific emphasis on the response to exogenous collagen matrix. In control cultures, albumin secretion increased during the first 7-10 days of culture to an average of 50 +/- 17 microg/day/10(6) cells and then decreased over the next 2 weeks. The pattern of urea synthesis was slightly different in that it was highest in the first 1-3 days postisolation (140 +/- 19 microg/day/10(6) cells) and then decreased by about 50% to a plateau level that was stable during the next 3-4 weeks of culture. Cytochrome P450-mediated activities were the most labile with time in culture and were undetectable after the first week in the absence of pharmacological inducers. In contrast to results reported for rat cells, porcine hepatocytes exhibited differentiated function in the absence of any modification of the culture dish surface and function was not increased or prolonged in the presence of exogenous collagen.
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PMID:In vitro characterization of porcine hepatocyte function. 1078 60

Five cases that were referred to the Division of Transplantation at NYU School of Medicine for consideration for liver transplantation were discussed among a panel of hepatitis B and liver transplant experts. Opinions were obtained on the management at every stage of treatment of patients with the following initial information: Case one: young Asian woman in stage IV hepatic coma; intubated; prothrombin time (PT): 30 s; serum glutamic oxaloacetic transaminase (SGOT): 8,000 IU; total bilirubin: 25 mg/dL; hepatitis B surface antigen (HBsAg) positive. Case two: 70-yr-old woman, native of Greece; decompensated cirrhosis with encephalopathy; Child-Pugh Class C; HBsAg positive; hepatitis B surface antibody (HBsAb) negative; hepatitis B e antigen (HBeAg) positive; hepatitis B e antibody (HBeAb) negative; hepatitis B virus (HBV) DNA titer: 10,000. Case three: Muscular detective working full-time; cirrhosis; Child Pugh Class B; ascites controlled with spironolactone and furosemide; PT: 19s; HBsAg positive; HBsAb negative; HBV DNA titer: 50,000; low platelet count. Case four: 45-yr-old baker; cirrhosis and resectable 4-cm hepatoma; Child-Pugh Class B; PT: 16 s; Blood type O; United Network for Organ Sharing (UNOS) 2B; HBV DNA titer: 3,000. Case five: 40-yr-old Indian man; 300 pounds with massive ascites; Child Pugh Class C; PT: 17 s; HBsAg positive; HBV DNA titer: 22,000; transplanted with intra-operative hypotension; tacrolimus; graft functioning; HBIg 10,000 IU intra-operative and around the clock during the first post-operative week; required huge doses of hepatitis B immune globulin (HBIg) to maintain adequate HBsAb level; daily loss of 5 6 L of ascites fluid; post-operative day 8: anuric, blood urea nitrogen (BUN) 127, creatinine 3, mental status changes.
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PMID:Case studies in orthotopic liver transplantation for hepatitis B: a panel discussion. 1096 64


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