Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Glycine N-methyltransferase deficiency is an inherited disorder of methionine metabolism, reported so far in only four patients and characterised by permanent hypermethioninemia. This disorder has been considered as probably benign because moderate hepatomegaly in two patients was the only obvious symptom and mild to moderate elevation of aminotransferases the only laboratory abnormality. Our experience with the current novel patient points out that this disease, due to very high hypermethioninemia, is not harmless and that there may be diagnostic pitfalls in interpretation of biochemical hallmarks of the disease. Since the first description of glycine N-methyltransferase deficiency, other disorders of this metabolic pathway affecting the liver have been reported pointing to dysmethylation as the common pathogenetic mechanism. Therefore, we suggest the whole group to be named dysmethylating liver diseases.
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PMID:Glycine N-Methyltransferase Deficiency: A Member of Dysmethylating Liver Disorders? 2720 70