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)

The Austrian Screening Program examined during 12 years 1,002.424 newborns and uncovered 23 cases of Galactosemia by Transferase deficiency, 6 by Kinase deficiency as well as 1 case of Phosphoglucomutase deficiency, 1 of porto-caval shunt and 1 congenital liver cirrhosis. Among the 23 Transferase deficiencies 18 took a fulminating course and 8 of these died. Since introduction of exchange transfusion as emergency treatment and acceleration of the screening procedure only 2 among 11 have died. Half of all Galactosemia cases, Transferase and Kinase, show already at the first examination (2. week) a cataract which however is reversible. In contrast to Kinase deficiency all cases of Transferase deficiency exhibit mental retardation if they grow older. Since treatment is early (9, 7 days), easy and the IQ already at 4 years 10 points below that of treated PKU's of same age a congenital brain damage has to be considered. Galactosemia by Transferase deficiency is in Western-Austria significantly more frequent than in Eastern-Austria. 17 boys compare with 6 girls. Among 6 cases of Galactosemia by Kinase deficiency 1 belonged to a Gippsy and 2 to Yugoslavian guest worker families. The 23 cases with Transferase deficiency had 45 siblings among whom 11 also were galactosemic. In 8 sibships the clinical course was of the same typ, but in 1 family one child showed the fulminating the other the subacute course.
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PMID:[Hypergalactosemia in newborns as uncovered by the Austrian screening program in 12 years (author's transl)]. 645 54

13C-phenylalanine (PheBT) and 13C-galactose breath tests (GBT) explore non invasively the hepatic functional mass by measuring two enzymatic activities localized into the cytosol of liver cells: the phenylalanine hydroxylase (which converts phenylalanine into tyrosine) and the galactose kinase (which catalyzes the ATP-dependent phosphorylation of galactose to galactose 1-phosphate). Both BTs are safe and accurate in predicting the severity of liver cirrhosis showing a good correlation with the Child-Pugh score. PheBT is also used in predicting postoperative complications and monitoring liver regeneration in patients undergoing partial hepatectomy. GBT has been also used to assess liver fibrosis in patients with chronic hepatitis C. PheBT and GBT could be used in the diagnosis of two inborn errors of metabolism, phenylketonuria and galactosemia, respectively. Both BTs are not affected by enzymatic induction due to drugs which may interfere with the results of the classic "microsomial" BTs (such as the aminopyrine or caffeine BTs).
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PMID:13C-breath tests in hepatology (cytosolic liver function). 1520 54

Multiple screening for aminoacidopathies has been attempted with a simple micromethod (Lancet, 2: 230, 1964) requiring only 10 mul. of plasma collected in a capillary tube and processed by a chromatographic technique. In a survey of 1250 infants, two newborn infants with phenylketonuria, two older infants with hypermethioninemia-tyrosinemia and hepatic cirrhosis were found, and approximately 10% of the premature infants had marked hypertyrosinemia. Multiple screening therefore has the advantage of multiple diagnosis over other techniques which screen specifically for a single disease. Pilot screening projects with this and other techniques could improve our knowledge of heritable metabolic disease so that mass screening for such problems may eventually be justifiable.
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PMID:A Commentary on Multiple Screening for Aminoacidopathies in the Newborn Infant. 2032 61

Physiological status and pathological changes in an individual can be captured by metabolic state that reflects the influence of both genetic variants and environmental factors such as diet, lifestyle and gut microbiome. The totality of environmental exposure throughout lifetime - i.e., exposome - is difficult to measure with current technologies. However, targeted measurement of exogenous chemicals and untargeted profiling of endogenous metabolites have been widely used to discover biomarkers of pathophysiologic changes and to understand functional impacts of genetic variants. To investigate the coverage of chemical space and interindividual variation related to demographic and pathological conditions, we profiled 169 plasma samples using an untargeted metabolomics platform. On average, 1,009 metabolites were quantified in each individual (range 906 - 1,038) out of 1,244 total chemical compounds detected in our cohort. Of note, age was positively correlated with the total number of detected metabolites in both males and females. Using the robust Qn estimator, we found metabolite outliers in each sample (mean 22, range from 7 to 86). A total of 50 metabolites were outliers in a patient with phenylketonuria including the ones known for phenylalanine pathway suggesting multiple metabolic pathways perturbed in this patient. The largest number of outliers (N=86) was found in a 5-year-old boy with alpha-1-antitrypsin deficiency who were waiting for liver transplantation due to cirrhosis. Xenobiotics including drugs, diets and environmental chemicals were significantly correlated with diverse endogenous metabolites and the use of antibiotics significantly changed gut microbial products detected in host circulation. Several challenges such as annotation of features, reference range and variance for each feature per age group and gender, and population scale reference datasets need to be addressed; however, untargeted metabolomics could be immediately deployed as a biomarker discovery platform and to evaluate the impact of genomic variants and exposures on metabolic pathways for some diseases.
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PMID:Assessment of coverage for endogenous metabolites and exogenous chemical compounds using an untargeted metabolomics platform. 3179 30