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)

The congenital lactic acidosis form a heterogeneous group of inborn errors that includes defects of gluconeogenesis, the pyruvate dehydrogenase complex, the Krebs cycle and the respiratory chain. These disorders are not easily classified because of the absence of specific metabolites, difficulties in providing suitable tissue specimens and technical problems with the enzyme assays. The commonest causes of lactic acidosis due to inborn errors are the deficiencies of glucose-6-phosphatase and fructose bisphosphatase, which present with hypoglycaemia, lactic acidosis and hepatomegaly. Pyruvate carboxylase and phosphoenolpyruvate deficiencies vary considerably in both clinical expression and biochemical findings. Neurological symptoms predominate in defects of the pyruvate dehydrogenase complex, and some cases of the spinocerebellar ataxias may be due to partial defects of the pyruvate and 2-oxoglutarate dehydrogenase complexes.
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PMID:Problems in the congenital lactic acidoses. 628 Sep 37

A baby with congenital lactic acidosis is described. The blood levels of lactic acid and alanine as well as the excretion of these compounds in the urine were largely elevated. Clinically the illness presented with vomiting, poor feeding, areflexia, muscular hypotonia and hepatomegaly. The baby died at the age of three months. The pyruvate dehydrogenase complex in cultured fibroblasts showed an activity of 14% of normal values.
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PMID:[Chronic infantile lactate acidosis]. 741 Jan 11

We report a new type of fatal mitochondrial disorder caused by selective deficiency of mitochondrial ATP synthase (ATPase). A hypotrophic newborn from a consanguineous marriage presented severe lactic acidosis, cardiomegaly and hepatomegaly and died from heart failure after 2 days. The activity of oligomycin-sensitive ATPase was only 31-34% of the control, both in muscle and heart, but the activities of cytochrome c oxidase, citrate synthase and pyruvate dehydrogenase were normal. Electrophoretic and western blot analysis revealed selective reduction of ATPase complex but normal levels of the respiratory chain complexes I, III and IV. The same selective deficiency of ATPase was found in cultured skin fibroblasts which showed similar decreases in ATPase content, ATPase hydrolytic activity and level of substrate-dependent ATP synthesis (20-25, 18 and 29-33% of the control, respectively). Pulse-chase labelling of patient fibroblasts revealed low incorporation of [(35)S]methionine into assembled ATPase complexes, but increased incorporation into immunoprecipitated ATPase subunit beta, which had a very short half-life. In contrast, no difference was found in the size and subunit composition of the assembled and newly produced ATPase complex. Transmitochondrial cybrids prepared from enucleated fibroblasts of the patient and rho degrees cells derived from 143B. TK(-)human osteosarcoma cells fully restored the ATPase activity, ATP synthesis and ATPase content, when compared with control cybrids. Likewise, the pattern of [(35)S]methionine labelling of ATPase was found to be normal in patient cybrids. We conclude that the generalized deficiency of mitochondrial ATPase described is of nuclear origin and is caused by altered biosynthesis of the enzyme.
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PMID:A novel deficiency of mitochondrial ATPase of nuclear origin. 1048 64