Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with carbamyl phosphate synthetase deficiency had four episodes of hyperammonemia, up to 226 microM, associated with valproate (VPA) treatment. These were accompanied by vomiting, lethargy, and coma. A group of epileptic patients receiving VPA remained asymptomatic but had significantly higher mean plasma ammonium levels when compared to epileptic patients receiving other anticonvulsants: 33.6 +/- 1.9 (SEM) versus 23.6 +/- 1.5 microM. Thus, VPA caused symptomatic hyperammonemia in a patient with an impairment in urea synthesis and resulted in mildly elevated ammonium levels in epileptic patients. These data suggest that ammonium levels should be monitored in patients receiving VPA who exhibit signs of vomiting or lethargy.
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PMID:Valproate-induced hyperammonemia. 680 93

(1) The concentrations of unconjugated and conjugated phenol, p-cresol, benzyl alcohol, catechol, hydroquinone, homocatechol, and 2-methoxyresorcinol in uremic serum were determined using a mass fragmentographic method. Concentrations of all phenols in uremic serum were higher than in normal serum. Conjugated phenols existed mainly as sulfate esters. (2) The concentration of unconjugated phenol in uremic serum correlated with those of serum creatinine and urea, but not with the hematocrit value. Patients with the highest concentration of unconjugated phenol suffered from cerebral disorders, coma or lethargy, and hemorrhagic tendencies. Unconjugated phenol was detected in normal serum at a concentration of 0.86 +/- 0.63 mumol/l (mean +/- S.D., n = 10). (3) The concentration of unconjugated p-cresol in uremic serum did not correlate with those of serum creatinine, urea and the hematocrit value. (4) The concentrations of unconjugated and conjugated hydroquinone in uremic serum correlated with those of serum creatinine and urea. (5) 2-Methoxyresorcinol was first detected mainly as sulfate ester in uremic serum at a concentration of 19 +/- 9.0 mumol/l (mean +/- S.D,. n = 17). (6) The daily excretion of eight unconjugated phenols into normal urine was determined.
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PMID:A gas chromatographic-mass spectrometric analysis for phenols in uremic serum. 721 14

11 adult female dogs were given periodic intravenous injections of uranyl nitrate [UO2(NO3)2 . 6H2O] to create a syndrome of chronic uremia. Initially, dogs usually received 2.0 mg/kg of uranyl nitrate; subsequent doses were generally less. After the initial injection, there was an abrupt fall in creatinine clearance and rise in plasma urea nitrogen. Low and relatively constant creatinine clearances (10.2 +/- SD 2.7 ml/min) were easily maintained with further injections. Dogs developed proteinuria, aminoaciduria, weight loss, and plasma amino acid levels similar to those of chronically uremic humans and rats. With creatinine clearances of 4 ml/min or less, dogs became listless and lethargic, and daily activity and food intake decreased. Repeated injections of uranyl nitrate appear to be an easy and reliable method for creating a model of chronic uremia in dogs.
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PMID:Chronic uremia syndrome in dogs induced with uranyl nitrate. 736 Feb 99

Ornithine transcarbamylase deficiency is an X-linked recessive disorder of urea biosynthesis characterized by recurrent, often fatal, hyperammonemic encephalopathy in affected males; carrier females are usually asymptomatic. We report here the clinical and laboratory findings in five symptomatic heterozygous females with ornithine transcarbamylase deficiency. In each case, the onset of symptoms occurred in the 1st year of life, but diagnosis was delayed by up to 15 years. Symptoms included recurrent vomiting with lethargy (five patients), dietary protein intolerance (five), irritability (four), severe acute encephalopathy (three), ataxia (three), and acute hemiparesis (two). All eventually showed evidence of developmental delay or learning difficulties. Two of the three who experienced severe, acute, hyperammonemic encephalopathy suffered serious, permanent neurologic sequelae. Three of the patients showed decreased ornithine transcarbamylase activity in liver obtained by needle biopsy, and the other two had marked orotic aciduria associated with hyperammonemia. Neuroimaging studies demonstrated persistent abnormal lobar attenuation and abnormal signal on computed tomographic scan and magnetic resonance imaging. All patients showed marked symptomatic improvement on treatment with dietary protein restriction supplemented by pharmacologic measures to increase nonprotein nitrogen excretion. Ornithine transcarbamylase deficiency should be considered in the differential diagnosis of acute or chronic encephalopathy in females at any age.
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PMID:Ornithine transcarbamylase deficiency in females: an often overlooked cause of treatable encephalopathy. 749 56

Adult female mink (Mustela vison) were fed a diet that contained Fusarium moniliforme culture material that provided dietary concentrations of 89 ppm fumonisin B1, 21 ppm fumonisin B2, and 8 ppm fumonisin B3 for 87 days. During the trial, there was mild lethargy in the mink fed fumonisins, but no other clinical signs or differences in feed consumption (measured during the first two weeks), body weights, or survivability were observed between the fumonisin-treated and control mink. Several hematologic parameters (mean corpuscular hemoglobin concentration, plasma total solids, and lymphocyte concentration) and serum chemical concentrations (globulin, phosphorus, potassium, blood urea nitrogen, creatinine, bilirubin, and cholesterol) and activities (alkaline phosphatase, alanine aminotransferase, amylase, and aspartate aminotransferase) were greater in the mink fed fumonisins than in the controls. Serum albumin/globulin and sodium/potassium ratios and chloride concentrations were lower in the fumonisin-fed mink than in the controls. The concentrations of free sphinganine and the ratio of free sphinganine to free sphingosine in the liver and kidneys of the fumonisin-treated mink were greater than in the control mink. No histopathologic alterations were associated with fumonisin treatment. These results indicate that long-term dietary exposure to F. moniliforme culture material containing 118 ppm total fumonisins is not lethal to adult mink, but can produce adverse physiological effects in the animals.
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PMID:Chronic toxicity of fumonisins from Fusarium moniliforme culture material (M-1325) to mink. 757 84

This article describes the metabolic investigations to be applied in any clinical situation consistent with a late acute form of inborn error of metabolism: unexplained coma with or without focal neurological manifestations, recurrent vomiting with lethargy, episodes of ataxia with or without behaviour disorder, fits of psychiatric troubles. In each of these situations, careful medical history is of major importance searching for previous clinical manifestations such as episodes of coma, ataxia or vomiting, anorexia, failure to thrive, developmental delay, all very suggestive of metabolic disorder. The association of neurological symptoms and abnormal hepatic tests is also of great value and must not lead to the diagnosis of Reye's syndrome without considering a metabolic defect of fatty acid oxidation, urea cycle, respiratory chain, or Wilson's disease. When looking for an etiological origin, it is mandatory to collect all the biological information at the same time, also knowing that metabolic abnormalities may be mild and transitory, and that many of them are non specific (metabolic acidosis, hyperlactacidemia, hyperammonemia, hepatic tests disturbances) being encountered in collapsus, shock and multiple organ failure syndrome.
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PMID:[Diagnosis of metabolic coma in children]. 784 29

One hundred fifty lactating mink on one ranch in southern Ontario were monitored over the lactation period in 1989 for evidence of clinical disease, and serial blood samples were collected for biochemical analysis. Antemortem blood samples were collected and necropsies performed on the 17 females that developed nursing disease and on 17 controls matched to the same stage of lactation and on ten nonlactating controls. Twenty-two additional nursing disease cases were selected from seven ranches in the following year and processed similarly. The clinical signs typically observed in affected females were sudden onset lethargy and anorexia followed by dehydration, ataxia, and a reluctance to move. The major clinical-pathologic findings were a marked increase in serum osmolality and total protein, urea nitrogen, creatinine, phosphorus, glucose, and potassium concentrations and a decrease in sodium and chloride concentration. In addition, the animals were acidotic, there was a reduction in the urine specific gravity, and the hemogram was consistent with a stress response. Emaciation and dehydration were the only pathologic changes consistently present in cases of nursing disease and not in controls. In almost all cases, bacteria were not cultured from the liver, spleen, and mammary gland, but Campylobacter jejuni was cultured from the intestinal contents of 15/17 affected mink and 2/5 controls. Aleutian disease virus antibody was not present in any of the affected mink. Lipid vacuoles in hepatocytes and renal tubular epithelium, hypertrophy of cells in the adrenal cortex, and pulmonary congestion and atelectasis were present in both diseased females and controls, as were various sporadic inflammatory lesions. Nursing disease may result from energy depletion due to lactation. All lactating females are affected by this process; clinical disease reflects the terminal physiologic decompensation of the most susceptible individuals.
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PMID:Nursing disease in mink: clinical and postmortem findings. 811 44

Ornithine transcarbamylase deficiency (OTCD) is caused by an alteration of urea synthesis, linked with partial modification of the X-chromosome, whose clinical manifestations are: lethargy, nausea, vomiting and cerebral edema. While in newborn males OTCD presents with hyperammoniemia leading to cerebral palsy with profound neurological impairment and eventually death, in women who are healthy carriers, it is possible to detect the disorder only through specific tests, since heterozygote women are rarely symptomatic. We describe the case of a young woman admitted to the hospital after an episode of mental confusion with vomiting and psychomotor restlessness, which had previously occurred several times during the premenstruum and lasted a few hours. A 2 day history of stupor made admission mandatory. Tests carried out during the hospital stay showed marked hyperammoniemia and unconjugated hyperbilirubinemia, marked cerebral edema documented by a CT scan. Liver biopsy and CSF test were normal. Screening of plasma and urinary aminoacids, level of orotic acid in the urine and OTC activity in the liver, confirmed the diagnosis of OTCD. The possibility of early diagnosis and therapy of a disease which otherwise leads to death, emphasizes the importance of precise evaluation of a possible organic cause of anorexia and behaviour disorders in young women.
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PMID:Hyperammoniemic coma in an adolescent girl: an unusual case of ornithine transcarbamylase deficiency. 828 23

A 24-year-old patient had symptoms of lethargy, convulsions and hyperammonaemia during valproic acid therapy. Cessation of valproic acid treatment brought about an improvement both of the symptoms and of the hyperammonaemia. However, enzymatic analysis after the cessation of valproic acid therapy revealed a complete absence of carbamoylphosphate synthetase (CPS) activity in liver biopsy. A unique polypeptide band, corresponding to the control CPS protein in molecular weight ('CPS-like' protein), was found in normal amounts in the patient's liver on sodium dodecyl sulphate-polyacrylamide gel electrophoresis. This CPS-like protein seemed to be more labile than the control, because the polypeptide band became faint after freeze-thawing. Intravenous administration of L-alanine resulted in a significant increase of serum urea and a transient increase of blood ammonia concentrations. These results strongly suggest that the patient has a labile CPS protein with no activity in vitro but some activity in vivo. We consider that valproic acid may have disrupted some metabolic adaptation by reducing N-acetylglutamate in the liver, which in combination with CPS deficiency induced severe hyperammonaemia.
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PMID:Carbamoylphosphate synthetase deficiency in an adult: deterioration due to administration of valproic acid. 848 2

A case of a 13-year-old boy with protracted vomiting, ataxia, and altered mental status, ultimately diagnosed with late-onset ornithine transcarbamylase (OTC) deficiency, is presented. OTC deficiency is the most common urea cycle defect and typically is diagnosed in male infants with irritability, poor feeding, vomiting, lethargy, and often death caused by the effects of hyperammonemia. Late-onset OTC deficiency has been described in patients of all ages. The presenting symptoms in these patients vary but the most common are vomiting and lethargy. The pathophysiology, clinical features, differential diagnosis, and treatment of this disorder are discussed. Because of the risks of serious consequences, early detection and treatment of OTC deficiency and hyperammonemic episodes are mandatory. Emergency physicians caring for children and adults need to be aware of the spectrum of clinical presentations of OTC deficiency, including late-onset disease.
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PMID:Vomiting, ataxia, and altered mental status in an adolescent: late-onset ornithine transcarbamylase deficiency. 885 3


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