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 study compares changes in the livers of rats treated with di(2-ethylhexyl) phthalate (DEHP) and its straight-chain analogs di(n-hexyl) phthalate (DnHP) and di(n-octyl phthalate (DnOP). Groups of rats were fed diets containing 20,000 ppm of one of these compounds. Subgroups were killed after 3, 10, and 21 days, and the livers were examined by histological, cytological, and biochemical methods. The results show considerable differences between the effects of the branched-chain phthalate ester DEHP and its straight-chain analogs. The major effects on the liver following administration of diets containing DEHP were midzonal and periportal accumulation of small droplets of lipid, hepatomegaly accompanied by an initial burst of mitosis, proliferation of hepatic peroxisomes and of smooth endoplasmic reticulum accompanied by induction of peroxisomal fatty acid oxidation, damage to the peroxisomal membranes as evidenced by increased leakage of catalase to the cytosol, and centrilobular loss of glycogen and falls in glucose-6-phosphatase activity and in low-molecular-weight reducing agents. In contrast, diets containing DnHP or DnOP induced accumulation of large droplets of fat around central veins leading, by 10 days, to mild centrilobular necrosis and a very slight induction of one peroxisomal enzyme and an increase in liver weight, but no significant changes in any other parameters which were affected by DEHP.
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PMID:Comparison of the short-term effects of di(2-ethylhexyl) phthalate, di(n-hexyl) phthalate, and di(n-octyl) phthalate in rats. 396 35

An 8-month-old female, maintained on breast feeding for 6 months, experienced numerous attacks of hyperventilation when weaned to baby food and was admitted with severe lactic acidosis (20 mM) and hypoglycemia. Physical examination was negative except for hepatomegaly. Fasting (18 hr) after stabilization on a high carbohydrate diet resulted in hypoglycemia (plasma glucose 40 mg/100 ml), lactic acidosis (6-10 mM), and a rise in plasma alanine. Glucagon produced a glycemic response after 6 hr, but not after 18 hr fasting. Intravenous galactose increased plasma glucose (Delta 45 mg/100 ml) but intravenous fructose, glycerol, and alanine caused a 40-50% fall in plasma glucose and a significant rise in lactate (Delta 3-4 mM). Liver biopsy showed fatty infiltration. Liver slices incubated with galactose, lactate, fructose, alanine, or glycerol converted only galactose to glucose. Hepatic glycolytic intermediates were increased below the level of fructose-1,6-diphosphate and decreased above. Hepatic phosphorylase, glucose-6-phosphatase, amylo-1,6-glucosidase, phosphofructokinase, fructose-1-phosphate aldolase, and fructose-1,6-diphosphate aldolase levels were normal, but no fructose-1,6-diphosphatase (FDPase) activity was detected. Further studies on the liver homogenate of this patient revealed the presence of an acid-precipitable activator of FDPase. Normal plasma glucose and lactate levels were maintained on an 800 cal diet of 66% carbohydrate (sucrose and fructose excluded). 5% protein, and 20% fat. When carbohydrate was reduced to 35% and protein or fat increased to 23 and 53% respectively, lactic acidosis and hypoglycemia recurred. These studies show that a deficiency of FDPase produced infantile lactic acidosis and hypoglycemia and can be controlled by an appropriate diet.
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PMID:Hepatic fructose-1,6-diphosphatase deficiency. A cause of lactic acidosis and hypoglycemia in infancy. 434 Oct 15

A girl presented with an important growth retardation, hepatomegaly, fasting hypoglycemia, lactic acidosis, increased serum cholesterol, triglycerides and uric acid, and increased liver glycogen (7.5%). There was no rise in blood glucose after IV galactose or fructose, but glucagon gave a delayed response. Type Ib glycogen storage disease was suggested by the low normal activity of glucose-6-phosphatase (G-6-Pase) which reached 1.8 units/g (normal, 2 to 10 units/g) and the normal activity of other glycogenolytic enzymes, measured in homogenates prepared in H2O (mean +/- S.E. in control subjects: 59% +/- 7; in type Ia GSD: 92% +/- 3). The activity of G-6-Pase measured as described above increased to 3.8 units/g of liver 1 year after PCS and 7.85 units/g of liver after 3 years. At that time, a simultaneous assay of the enzyme in a fresh, previously not frozen liver biopsy, homogenized in 0.25 M sucrose, revealed only about 29% of the activity of the same sample prepared in H2O (mean +/- S.E. in three controls: 95.8% +/- 8.9.
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PMID:Clinical and biochemical findings before and after portacaval shunt in a girl with type Ib glycogen storage disease. 625 80

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

Glycogen storage disease type Ib has all the clinical manifestations of glycogen storage disease type Ia such as hepatomegaly, growth retardation, bleeding tendency, hypoglycemia, hyperlactacidemia, hyperuricemia, hyperlipidemia, impaired platelet function plus neutropenia. The overall glucose-6-phosphatase activity in disrupted microsomes from liver is normal whereas glucose-6-phosphate translocase, the first enzyme in the glucose-6-phosphate transport system is absent. There is no glucose-6-phosphatase activity in vivo. Recent results show that in granulocytes the glucose-6-phosphate-dependent hexosemonophosphate-shunt is impaired.
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PMID:Glycogen storage disease type Ib. 631 72

A 5-year-old Black boy presented with massive hepatomegaly and muscle weakness. Liver biopsy revealed the presence of glycogen pools in the cytoplasm and nuclei of hepatocytes. Erythrocyte glycogen levels, identified as limit dextrin, were grossly increased. The galactose tolerance test as well as the two-stage glucagon stimulation test suggested a decrease in activity of both amylo-1,6-glucosidase and glucose-6-phosphatase enzymes. This was confirmed by direct assays performed on liver tissue and erythrocytes. The decrease in glucose-6-phosphatase activity was attributed to a secondary effect of limit dextrin.
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PMID:Glycogen storage disease type III. A case report. 632 Apr 74

Type IB Glycogen storage disease (GSD) is a new variant of type I Glycogen storage disease. It is characterized by same clinical findings: hepatomegaly, fasting hypoglycemia, hyperlipidemia, hyperuricemia, lactic acidosis, renal enlargement, short stature; but it distinguish for normal glucose-6-phosphatase hepatic activity in vitro. The involvement is in G-6-P transport system. Recently has been described in some patients with GSD IB, neutropenia and defective neutrophil mobility. In this report the authors described two family cases of GDS IB that one characterized by severe neutropenia.
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PMID:[Neutropenia in glycogenesis I B]. 659 20

Glycogen storage disease type 1b is a rare metabolic disorder which affects the transport system of glucose-6-phosphatase metabolism. As a result, hepatomegaly, failure to thrive, renal dysfunction and recurrent infections occur in affected patients. In this paper, the oral complications in three children with glycogen storage disease type 1b are discussed. Oral ulcers were a common finding, probably due to severe neutropenia and impaired neutrophil migration which characterises the onset of this rare disorder.
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PMID:Oral manifestations in glycogen storage disease type 1b. 777 66

Hepatic glycogen storage diseases (GSD) are a group of rare genetic disorders in which glycogen cannot be metabolized to glucose in the liver because of one of a number of possible enzyme deficiencies along the glycogenolytic pathway. Patients with GSD are usually diagnosed in infancy or early childhood with hypoglycemia, hepatomegaly, poor physical growth, and a deranged biochemical profile. Dietary therapies have been devised to use the available alternative metabolic pathways to compensate for disturbed glycogenolysis in GSD I (glucose-6-phosphatase deficiency), GSD III (debrancher enzyme deficiency), GSD VI (phosphorylase deficiency, which is less common), GSD IX (phosphorylase kinase deficiency), and GSD IV (brancher enzyme deficiency). In GSD I, glucose-6-phosphate cannot be dephosphorylated to free glucose. Managing this condition entails overnight continuous gastric high-carbohydrate feedings; frequent daytime feedings with energy distributed as 65% carbohydrate, 10% to 15% protein, and 25% fat; and supplements of uncooked cornstarch. In GSD III, though glycogenolysis is impeded, gluconeogenesis is enhanced to help maintain endogenous glucose production. In contrast to treatment for GSD I, advocated treatment for GSD III comprises frequent high-protein feedings during the day and a high-protein snack at night; energy is distributed as 45% carbohydrate, 25% protein, and 30% fat. Patients with GSD IV, VI, and IX have benefited from high-protein diets similar to that recommended for patients with GSD III.
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PMID:Nutrition therapy for hepatic glycogen storage diseases. 824 77

A male child presented at 5 months of age with vomiting, diarrhoea, hypoglycaemia and hepatomegaly. Histology on a frozen liver biopsy suggested glycogen storage disease (GSD), while biochemical analyses confirmed an elevated glycogen content and normal activities of the GSD enzymes with the proviso that a variant of GSD 1 should be considered. The patient presented at 9 months of age with severe lactic acidosis and hypoglycaemia. A glucagon tolerance test and galactose load test on the patient produced no glycaemic response. A second biopsy was obtained and appropriately handled for the investigation of variants of the glucose-6-phosphatase enzyme (G6Pase) complex. Results showed that the patient had a deficiency of two transport proteins of the G6Pase complex, namely glucose-6-phosphate translocase and pyrophosphate translocase, i.e. GSD 1b/1c beta. These results were confirmed by additional kinetic analyses which provided confirmation of the double translocase deficiency. Evidence for inhibitors to these translocases was not found. The patient's treatment has resulted in the hypoglycaemia now being well controlled; however, at 3 years of age, height and weight are markedly lagging and he is moderately developmentally delayed. Neutropenia has not been found and neutrophil function is normal. Double enzyme deficiencies are very rare and possible explanations which might lead to this phenotype are considered. This, to the authors' knowledge, is the first report of a double translocase deficiency causing GSD type 1.
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PMID:Multiple transport protein defects in a patient with glycogen storage disease type 1: GSD 1b/1c beta. 859 36


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