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 results of biochemical studies in three children with cholesterol ester storage disease are reported. This rare disease (13 published cases) and the related Wolman's disease are characterised by a deficiency of acid lipase. Affected children mostly present with isolated hepatomegaly. Hepatic cells (one patient) and fibroblasts (two patients) were cultured and cholesterol accumulation measured. Hepatic cells contained more cholesterol than fibroblasts but the enzyme deficiency, assessed by the abnormal degree of esterification was the same in both cell types.
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PMID:[Cholesterol ester storage disease in children. Comparative biochemistry of hepatocyte and fibroblast cultures]. 74 52

Cholesteryl ester storage disease, caused by the loss of lysosomal acid ester hydrolase (EC 3.1.1.13), has been previously associated with hyperlipidemia and premature atherosclerosis. We identified a 23-month-old female with cholesteryl ester storage disease and characterized the plasma lipids and lipoproteins in the proband and her family. These studies illustrate several important points about this disease. First, a high index of suspicion is required to diagnose this disease since the major physical manifestation of the disorder, mild hepatomegaly, is subtle. Second, the Type II hyperlipoproteinemia in the proband is paralleled by a reduction in the concentration of high density lipoproteins. Third, analysis of the plasma lipids and lipoproteins in family members revealed both Type II and Type IV hyperlipoproteinemia with an inheritance pattern similar to that of familial combined hyperlipoproteinemia. Fourth, the parents and brother of this patient had 50% normal fibroblast acid ester hydrolase activity. These results raise the possibility that deficiency of the lysosomal acid ester hydrolase may be linked to familial combined hyperlipoproteinemia and that this enzyme deficiency may be more common than previously appreciated.
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PMID:Characterization of plasma lipids and lipoproteins in cholesteryl ester storage disease. 399 99

The lysosomal enzyme responsible for cholesteryl ester hydrolysis, acid cholesteryl ester hydrolase, or acid lipase (E.C.3.1.1.13) plays an important role in cellular cholesterol metabolism. Loss of the activity of this enzyme in tissues of individuals with both Wolman disease and cholesteryl ester storage disease is believed to play a causal role in these conditions. The objectives of our studies were not only to directly compare and contrast the clinical features of Wolman disease and cholesteryl ester storage disease but also to determine the reasons(s) for the varied phenotype expression of acid cholesteryl ester hydrolase deficiency. Although both diseases manifest a type II hyperlipoproteinemic phenotype and hepatomegaly secondary to lipid accumulation, a more malignant clinical course with more significant hepatic and adrenal manifestations was observed in the patient with Wolman disease. However, the acid cholesteryl ester hydrolase activity in cultured fibroblasts in both diseases was virtually absent. In addition, fibroblasts from both Wolman disease and cholesteryl ester storage disease were able to utilize exogenously supplied enzyme, suggesting that neither disease was due to defective enzyme delivery by the mannose-6-phosphate receptor pathway. Coculture and cell fusion of fibroblasts from Wolman disease and cholesteryl ester storage disease subjects did not lead to correction of the enzyme deficiency, indicating that these disorders are allelic. However, the activities of the hepatic acid and neutral lipase in these two clinical variants were quite different. Hepatic acid lipase activity was only 4% normal in Wolman disease, but the activity was 23% normal in cholesteryl ester storage disease. The hepatic neutral lipase activity was normal in Wolman disease but increased more than twofold in cholesteryl ester storage disease. These combined results indicate that the clinical heterogeneity in acid cholesteryl ester hydrolase deficiency can be explained by a varied hepatic metabolic response to an allelic mutation.
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PMID:Cholesteryl ester storage disease and Wolman disease: phenotypic variants of lysosomal acid cholesteryl ester hydrolase deficiency. 609 11

This is a report on a child with a syndrome characterized by an extensive congenital ichthyosiform eruption, neurosensory deafness and abnormally elevated serum steroid disulfates neonatally. When analysed by gas-liquid chromatography (glc) and gas chromatography-mass spectrometry (gc-ms) the following serum steroid disulfates were very high 5 days after birth: 5-androstene-3 beta,17 alpha-diol (56 micrograms/ml), 5-androstene-3 beta,17 beta-diol (25 micrograms/ml) and 5-pregnene-3 beta,20 alpha-diol (26 micrograms/ml). The values are about one hundred times higher than the reference values at this age. At the same time serum steroid monosulphate concentrations were normal. The patient had normal steroid sulfatase activity in skin biopsies, indicating that enzyme deficiency was not the reason for the high steroid disulfate concentrations. When serum steroid disulphatases were next analysed at 16 months of age they were normal. No hepatomegaly was observed but the other laboratory data support the hypothesis that the serum steroid disulphate concentrations were due to neonatal hepatography. Later, no indications of chronic liver disease were observed. These indications have not been described earlier in ichthyosiform erythrodermia and it is possible that the patient represents a new type of this rare disease.
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PMID:A congenital ichthyosiform syndrome with deafness and elevated serum steroid disulphate levels. 616 35

In a 4.5-month-old boy presenting with marked muscular hypotonia in the neonatal period, hepatomegaly, cardiac hypertrophy, recurrent hypoglycemia, metabolic acidosis, and secondary carnitine deficiency, there was a considerable urinary excretion of 3-methylglutaconic and 3-methylglutaric acid. Estimation of 3-methylglutaconyl-CoA hydratase, 3-hydroxy-3-methylglutaryl-CoA lyase and initial enzymatic steps of cholesterol biosynthesis in cultured fibroblasts and in different tissues postmortem revealed no enzyme deficiency. Analyses of the respiratory chain in postmortem tissues demonstrated severe impairment of complex I (NADH ubiquinone oxidoreductase) and complex IV (cytochrome c oxidase) activities in skeletal muscle and reduced complex IV activity in heart.
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PMID:Multiple respiratory chain abnormalities associated with hypertrophic cardiomyopathy and 3-methylglutaconic aciduria. 769 3

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

We describe four infants with a novel subtype of an isolated deficiency of one of the peroxisomal beta-oxidation enzymes with detectable enzyme protein. The patients showed characteristic clinical and biochemical abnormalities, including hypotonia, psychomotor retardation, hepatomegaly, typical facial appearance, accumulation of very-long-chain fatty acids, and decreased lignoceric acid oxidation. However, beta-oxidation enzyme proteins were detected by immunoblot analyses, and large peroxisomes were identified by immunofluorescence staining. In order to identify the underlying defect in these patients, complementation analysis was introduced using fibroblasts from these patients and patients with an established deficiency of either acyl-CoA oxidase or bifunctional enzyme, as identified by immunoblotting. In the complementing combinations, fused cells showed increased lignoceric acid oxidation, resistance against 1-pyrene dodecanoic acid/UV selection, and normalization of the size and the distribution of peroxisomes. The results indicate that two patients with a more severe clinical course were suffering from bifunctional enzyme deficiency and that the other two infants, who were siblings and had a less severe clinical presentation, were the first patients with acyl-CoA oxidase deficiency with detectable enzyme protein.
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PMID:Novel subtype of peroxisomal acyl-CoA oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein: identification by means of complementation analysis. 827 68

Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20000-43000 live births. There are over 12 types and they are classified based on the enzyme deficiency and the affected tissue. Disorders of glycogen degradation may affect primarily the liver, the muscle, or both. Type Ia involves the liver, kidney and intestine (and Ib also leukocytes), and the clinical manifestations are hepatomegaly, failure to thrive, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia. Type IIIa involves both the liver and muscle, and IIIb solely the liver. The liver symptoms generally improve with age. Type IV usually presents in the first year of life, with hepatomegaly and growth retardation. The disease in general is progressive to cirrhosis. Type VI and IX are a heterogeneous group of diseases caused by a deficiency of the liver phosphorylase and phosphorylase kinase system. There is no hyperuricemia or hyperlactatemia. Type XI is characterized by hepatic glycogenosis and renal Fanconi syndrome. Type II is a prototype of inborn lysosomal storage diseases and involves many organs but primarily the muscle. Types V and VII involve only the muscle.
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PMID:Glycogen storage diseases: new perspectives. 1755 1

A 14-month-old female infant presented with recurrent episodes of acute gastroenteritis accompanied by severe metabolic acidosis and hypoglycemia. Physical examination showed hepatomegaly. Laboratory evaluation revealed elevated hepatic enzymes, prolonged prothrombin time, hyperuricemia, and extremely elevated lactate and alanine levels. Glucagon injection during hypoglycemia resulted in a further decrease of blood glucose. She was treated with glucose-containing intravenous fluids, with rapid improvement and normalization of her blood pH and glucose levels. Hormonal assessment during two episodes of hypoglycemia indicated growth hormone (GH) deficiency. However, as isolated GH deficiency could not explain all other concomitant features, such as severe lactic acidosis, hepatomegaly, impaired liver function, and hyperuricemia, the possibility of a combined defect was suggested. Further lymphocytic enzymatic investigation revealed fructose-1,6-diphosphatase deficiency and molecular genetic analysis demonstrated frame shift mutation in the FBP1 gene. This enzyme deficiency causes a rare metabolic disorder not previously described in combination with GH deficiency.
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PMID:Recurrent infantile hypoglycemia due to combined fructose-1,6-diphosphatase deficiency and growth hormone deficiency. 2358 10

Sialidoses are autosomal recessive disorders caused by NEU1 gene mutations and are classified on the basis of their phenotype and onset age. Sialidosis type II, with infantile onset, has a more severe phenotype characterized by coarse facial features, hepatomegaly, dysostosis multiplex, and developmental delay while patients with the late and milder type, known as "cherry red spot-myoclonus syndrome" develop myoclonic epilepsy, visual impairment and ataxia in the second or third decade of life. The diagnosis is usually suggested by increased urinary bound sialic acid excretion. We recently described genetically diagnosed patients with a specially mild phenotype, no retinal abnormalities and normal urinary sialic acid. This observation suggests that genetic analysis or the demonstration of the neuraminidase enzyme deficiency in cultured fibroblasts are needed to detect and diagnose mildest phenotypes.
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PMID:Sialidoses. 2762 Nov 98


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