Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We successfully anesthetized a 53-year-old female with hypercitrullinemia and severe liver cirrhosis. The hypercitrullinemia was accompanied with chronic hepatic encephalopathy due to hyperammonemia, which resulted from decreased activity of one of the urea cycle enzymes, argininosuccinate synthetase (ASS). She was scheduled for replacement arthroplasty of a fractured femoral neck. She suffered a consciousness disturbance due to hyperammonemia, which was successfully treated by oral administration of sodium benzoate before surgery. Spinal anesthesia was chosen because it would have the minimum metabolic load on the cirrhotic liver. During the operation, prostaglandin was continuously infused to maintain hepatic blood flow. Acetated Ringer solution was infused instead of lactated Ringer solution to reduce metabolic load on the liver. She was given a small dose each of fentanyl and midazolam for relief of pain and sedation. After the operation, naloxone and flumazenil were administered to antagonize the fentanyl and midazolam, respectively. Although the serum ammonia level temporarily increased during a postoperative interruption of oral administration of sodium benzoate, the patient did not develop loss of consciousness, which is a key sign of hyperammonemia. Surgery and anesthesia were uneventfully completed.
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PMID:[Anesthetic management for a patient with citrullinemia and liver cirrhosis]. 769 32

Type II citrullinemia (CTLN2) is characterized by a deficiency of argininosuccinate synthetase (ASS) in the liver. Mutation analysis of the SLC25A13 gene, which is responsible for CTLN2, provides a rapid and accurate diagnosis. We describe clinical, biochemical and histologic features of two patients, whose diagnosis was finally made by mutation analysis. They initially presented with symptoms related to hyperammonemia at 16 to 22 years of age. A patient had shown mental retardation and growth failure from early childhood. Laboratory findings including amino acids, were characteristic, such as elevated citrulline, arginine, and lysine concentrations, but definitive diagnosis had not been made. The patients died of liver cirrhosis and hepatoma at 31 and 34 years old, respectively. Fatty change in the hepatocytes was commonly observed in the autopsied specimens. ASS activity was decreased in the liver of both patients, and a concomitant decrease of arginase activity was found in one case. Investigation for the SLC25A13 mutation revealed that one patient was homozygous for IVS11 + 1G>A, and the other was compound heterozygote (851del4/S225X). Comparison of genetic, enzymatic and biochemical data among various cases of CTLN2 will be essential to understand the real nature of the disease.
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PMID:Application of mutation analysis for the previously uncertain cases of adult-onset type II citrullinemia (CTLN2) and their clinical profiles. 1251 93

We report the first pharmacokinetic and clinical response data from a patient with unresectable hepatocellular cancer treated with a new drug, ADI PEG20,000 mw (arginine deiminase-polyethylene glycol 20,000 molecular weight). A single patient with idiopathic cirrhosis and unresectable hepatocellular cancer was treated with escalating dosages of ADI-PEG20,000 mw. Human hepatocellular cancer has been found to be arginine-dependent for growth because of loss of expression or arginosuccinate synthetase, the rate-limiting enzyme in the conversion of citrulline to arginine. Thus, an arginine-degrading enzyme like ADI-PEG20,000 mw should produce cell death in hepatocellular cancer cells without significantly affecting normal cells. There was a dose-dependent reduction of plasma arginine levels after weekly intramuscular administration of ADI-PEG20,000 mw. Successive treatment cycles at the optimal biologic dose of 160 IU/m2 led to reduction in tumor size and serum alpha-fetoprotein levels. Sufficient tumor cytoreduction was achieved with ADI-PEG20,000 mw treatment to permit surgical treatment. The patient developed no toxicities or side effects related to ADI-PEG20,000 mw treatment. The results in a single patient with unresectable hepatocellular cancer treated with ADI-PEG20,000 mw suggests this may be a promising, low-toxicity treatment. Full-scale clinical trials have been initiated.
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PMID:Regression of hepatocellular cancer in a patient treated with arginine deiminase. 1457 1

A 17-month-old girl with type I classical citrullinaemia (CTLN1) presenting with early cirrhosis and unusual ultrastructural features of the liver is reported. The patient is homozygous for a splicing mutation in intron 15 of the argininosuccinate synthase gene.
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PMID:Early cirrhosis in a patient with type I citrullinaemia (CTLN1). 1533 37

Adult-onset citrullinemia (CTLN2) is a rare hereditary metabolic disorder characterized by highly increased concentration of citrulline and ammonia in the plasma, which is ascribed to a deficiency of argininosuccinate synthetase (ASS), one of the urea cycle enzymes mainly located in the liver. Neurological manifestation in CTLN2 patients closely resemble those of hepatic encephalopathy and in the past, most patients usually followed rapidly deteriorating clinical courses and died of severe brain edema within a few years after onset. However, in 1995 the first CTLN2 patient who was successfully treated by living-related liver transplantation was reported and since then more than 30 patients had underwent this operation in our country, showing good outcomes. No primary defect had not been found within ASS gene locus, but the causative gene of this disorder is now identified as the "citrin gene", which might act as a aspartate/glutamate transporter in mitochondria. Different phenotypes are seen in the individuals with a citrin deficiency: neonatal intrahepatic cholestasis, juvenile-onset chronic pancreatitis and hepatocellular carcinoma without cirrhosis can precede the appearance of CTLN2. The precise pathogenesis of this disease that includes the relationship between the mutations of citrin gene and a deficiency of hepatic ASS activity remains unclear.
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PMID:[Adult-onset citrullinemia]. 1722 80

Adult-onset citrullinemia (CTLN2) is a rare hereditary metabolic disorder characterized by highly increased concentration of citrulline and ammonia in the plasma, which is ascribed to a deficiency of argininosuccinate synthetase (ASS), one of the urea cycle enzymes mainly located in the liver. Neurological manifestation in CTLN2 patients closely resemble those of hepatic encephalopathy and in the past, most patients usually followed rapidly deteriorating clinical courses and died of severe brain edema within a few years after onset. However, in 1995 the first CTLN2 patient who was successfully treated by living-related liver transplantation was reported and since then more than 30 patients had underwent this operation in our country, showing good outcomes. No primary defect had not been found within ASS gene locus, but the causative gene of this disorder is now identified as the "citrin gene", which might act as a aspartate/glutamate transporter in mitochondria. Different phenotypes are seen in the individuals with a citrin deficiency: neonatal intrahepatic cholestasis, juvenile-onset chronic pancreatitis and hepatocellular carcinoma without cirrhosis can precede the appearance of CTLN2. The precise pathogenesis of this disease that includes the relationship between the mutations of citrin gene and a deficiency of hepatic ASS activity remains unclear.
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PMID:[Adult-onset citrullinemia]. 1735 80