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)

Hepatomegaly is an important clinical finding in patients with argininosuccinic aciduria (a hereditary defect of the urea cycle enzyme, argininosuccinate lyase [argininosuccinase]). A severe degree of liver fibrosis, almost corresponding to cirrhosis, was observed in liver biopsy material obtained from a boy with this disorder. This observation is of interest in light of the fact that liver fibrosis or cirrhosis are hallmarks of many inheritable phenotypes, and especially of inborn errors of metabolism. Variable degrees of liver fibrosis are noted in other inborn defects of the urea cycle, eg, in ornithine transcarbamylase and carbamoylphosphate synthetase deficiencies. These findings appear to indicate that inheritable defects of urea synthesis may form a group of metabolic disorders prone to cause hepatic fibrosis, or even cirrhosis, as shown in our patient.
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PMID:Severe liver fibrosis in argininosuccinic aciduria. 375 45

Late onset of symptoms in a 12 1/2-year-old male with ornithine transcarbamylase (OTC) deficiency were associated with unusual histological features in the liver. The patient presented with an acute onset of hyperammonemia and altered mental status after a 2-day prodrome of vomiting and lethargy. Physical examination showed a combative and disoriented male with icteric sclerae but with no fever or hepatomegaly. The plasma ammonia level was 282 microM. Enzyme assays of liver tissue obtained by percutaneous needle biopsy showed OTC activity of approximately 3% of normal; carbamyl phosphate synthetase was normal. Histopathological findings included severe microvesicular centrilobular steatosis. Hepatic architecture and reticulin framework were well preserved. Many hepatocyte nuclei were filled with glycogen. Electron microscopy showed mitochondria that were rounded and expanded with cristae at the edge of the mitochondrial membrane. In contrast to other reports, only slight variations in size and shape were seen. Megamitochondria and intramatrical paracrystalline inclusions were not identified. The cytoplasm contained scattered fat globules, peroxisomes, and dilated smooth endoplasmic reticulum. The prominent mitochondrial abnormalities commonly found in OTC deficiency were notably absent.
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PMID:Histopathological findings in a male with late-onset ornithine transcarbamylase deficiency. 800 87

Mouse models for urea cycle disorders have been available for the past 30 y; however, until now, no measurements of urea production in vivo have been conducted. Urea entry rate was determined in Otc(spf-ash) and littermate controls employing a primed-continuous infusion of 15N15N urea. A saline infusion control, a complete mixture of amino acids (AA), or a glycine-alanine (GA) mixture was infused at 86 (AA1 and GA1) and 172 mg N.kg(-1).h(-1) (AA2 and GA2) to impose a defined nitrogen load on the urea cycle. Urea entry rate and plasma urea concentration increased (P < 0.001) as a consequence of the increase in the infusion rate of the complete mixture of amino acids, but the 2 genotypes did not differ (P = 0.96 and P = 0.44, respectively). The infusion of the GA mixture, however, decreased (P < 0.001) the plasma urea concentration and urea entry rate in Otc(spf-ash) mice compared with controls. At the highest level (GA2), urea entry rate was further depressed (P < 0.001), Otc(spf-ash) mice became hyperammonemic (1701 +/- 150 micromol/L), and hyperammonemic symptoms were evident. An acute hepatic enlargement (P < 0.001) was also evident in Otc(spf-ash) mice infused with GA2. These results show that despite vestigial OTC activity, Otc(spf-ash) mice were able to maintain ureagenesis at the same rate of control animals when a complete mixture of amino acids was infused. This implies that Otc(spf-ash) mice are able to dispose of ammonia, without apparent adverse effects, when a balance mixture of amino acids is provided, despite reduced enzyme activity.
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PMID:Reduced ornithine transcarbamylase activity does not impair ureagenesis in Otc(spf-ash) mice. 1654 67