Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We discuss an infant with hepatitis and hypermethioninemia. An inborn error of metabolism, such as methionine adenosyltransferase deficiency or hereditary tyrosinemia, was originally thought to be the basis for these abnormalities. The infant's subsequent clinical course, however, was incompatible with such a diagnosis; the hypermethioninemia was instead due to the trilogy of prematurity, hepatitis, and a high-protein, high-methionine diet.
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PMID:Hypermethioninemia in an infant. 56 5

This paper reports clinical and metabolic studies of two Italian siblings with a novel form of persistent isolated hypermethioninaemia, i.e. abnormally elevated plasma methionine that lasted beyond the first months of life and is not due to cystathionine beta-synthase deficiency, tyrosinaemia I or liver disease. Abnormal elevations of their plasma S-adenosylmethionine (AdoMet) concentrations proved they do not have deficient activity of methionine adenosyltransferase I/III. A variety of studies provided evidence that the elevations of methionine and AdoMet are not caused by defects in the methionine transamination pathway, deficient activity of methionine adenosyltransferase II, a mutation in methylenetetrahydrofolate reductase rendering this activity resistant to inhibition by AdoMet, or deficient activity of guanidinoacetate methyltransferase. Plasma sarcosine (N-methylglycine) is elevated, together with elevated plasma AdoMet in normal subjects following oral methionine loads and in association with increased plasma levels of both methionine and AdoMet in cystathionine beta-synthase-deficient individuals. However, plasma sarcosine is not elevated in these siblings. The latter result provides evidence they are deficient in activity of glycine N-methyltransferase (GNMT). The only clinical abnormalities in these siblings are mild hepatomegaly and chronic elevation of serum transaminases not attributable to conventional causes of liver disease. A possible causative connection between GNMT deficiency and these hepatitis-like manifestations is discussed. Further studies are required to evaluate whether dietary methionine restriction will be useful in this situation.
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PMID:Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia. 1159 49

We report studies of a Greek boy of gypsy origin that show that he has severe deficiency of glycine N -methyltransferase (GNMT) activity due to apparent homozygosity for a novel mutation in the gene encoding this enzyme that changes asparagine-140 to serine. At age 2 years he was found to have mildly elevated serum liver transaminases that have persisted to his present age of 5 years. At age 4 years, hypermethioninaemia was discovered. Plasma methionine concentrations have ranged from 508 to 1049 micro mol/L. Several known causes of hypermethioninaemia were ruled out by studies of plasma metabolites: tyrosinaemia type I by a normal plasma tyrosine and urine succinylacetone; cystathionine beta-synthase deficiency by total homocysteine of 9.4-12.1 micro mol/L; methionine adenosyltransferase I/III deficiency by S -adenosylmethionine (AdoMet) levels elevated to 1643-2222 nmol/L; and S -adenosylhomocysteine (AdoHcy) hydrolase deficiency by normal AdoHcy levels. A normal plasma N -methylglycine concentration in spite of elevated AdoMet strongly suggested GNMT deficiency. Molecular genetic studies identified a missense mutation in the coding region of the boy's GNMT gene, which, upon expression, retained only barely detectable catalytic activity. The mild hepatitis-like manifestations in this boy are similar to those in the only two previously reported children with GNMT deficiency, strengthening the likelihood of a causative association. Although his deficiency of GNMT activity may well be more extreme, his metabolic abnormalities are not strikingly greater. Also discussed is the metabolic role of GNMT; several additional metabolite abnormalities found in these patients; and remaining questions about human GNMT deficiency, such as the long-term prognosis, whether other individuals with this defect are currently going undetected, and means to search for such persons.
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PMID:Glycine N -methyltransferase deficiency: a new patient with a novel mutation. 1473 80

S-adenosyl-L-methionine (SAM) is synthesized by methionine adenosyltransferases (MATs). Ablation of the liver-specific MAT1A gene results in liver neoplasia and sensitivity to oxidant injury. Here we show that acidic sphingomyelinase (ASMase) mediates the downregulation of MAT1A by TNF-alpha. The levels of MAT1A mRNA as well as MAT I/III protein decreased in cultured rat hepatocytes by in situ generation of ceramide from exogenous human placenta ASMase. Hepatocytes lacking the ASMase gene (ASMase-/-) were insensitive to TNF-alpha but were responsive to exogenous ASMase-induced downregulation of MAT1A. In an in vivo model of lethal hepatitis by TNF-alpha, depletion of SAM preceded activation of caspases 8 and 3, massive liver damage, and death of the mice. In contrast, minimal hepatic SAM depletion, caspase activation, and liver damage were seen in ASMase-/- mice. Moreover, therapeutic treatment with SAM abrogated caspase activation and liver injury, thus rescuing ASMase+/+ mice from TNF-alpha-induced lethality. Thus, we have demonstrated a new role for ASMase in TNF-alpha-induced liver failure through downregulation of MAT1A, and maintenance of SAM may be useful in the treatment of acute and chronic liver diseases.
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PMID:Acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor-induced lethal hepatitis. 1506 22

Chronic hepatitis C virus (HCV) infection is a worldwide public health problem with a global prevalence of 2-3%. It is believed that about 170 million people are currently infected (about 3% of the world's population), and a further 3-4 million are infected each year. HCV is the main reason for liver transplantation in the developed world, and the main cause of liver-related morbidity and mortality in a number of countries, including Italy. It is not only a frequent cause of chronic liver diseases such as hepatitis, cirrhosis and hepatocellular carcinoma, but is also involved in the pathogenesis of various autoimmune and rheumatic disorders (arthritis, vasculitis, sicca syndrome, porphyria cutanea tarda, lichen planus, nephropathies, thyroid diseases, and lung fibrosis), as well as in the development of B-cell lymphoproliferative diseases. Furthermore, patients suffering from C hepatitis tend to produce rheumatoid factor, cryoglobulins and a large series of autoantibodies (ANA, anti-SSA/SSB, SAM, ATG, aCL). The use of glucocorticoids or immuno-suppressant agents in HCV infected individuals, which are needed to treat autoimmune and rheumatic disorders, leads to a risk of worsening the clinical outcome of HCV. Under these conditions, the viral infection often needs to be treated with antiviral agents, mainly pegylated interferon combined with ribavirin. However, cyclosporine A seems to be safe and effective in patients with autoimmune disease (AD) and concomitant chronic HCV infection as is documented by the reduction in viremia and transaminases, particularly in patients with high baseline levels. Finally, HCV is the main trigger of mixed cryoglobulinemia. An attempt at viral eradication is therefore indicated in most patients, and is particularly effective in the case of mild or moderate manifestations. In severe cases, rituximab is an apparently safe and effective alternative to conventional immunosuppression and, specifically, it controls B-cell proliferation.
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PMID:HCV infection: pathogenesis, clinical manifestations and therapy. 1857 Jul 53