Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
PMID:[Cholesterol ester storage disease in children. Comparative biochemistry of hepatocyte and fibroblast cultures]. 74 52

Of three siblings affected with cholesterol ester storage disease, two died at ages 7 and 9 years, respectively, with hepatic scarring and portal hypertension. Lipid storage was documented in both patients, as were esophageal varices and aortic plaques in the older child. The third affected sibling, followed to 13 years of age, has hepatomegaly, hyperlipidemia, short stature, adrenal calcification, and acid lipase deficiency. Leukocyte extracts demonstrated deficiency of acid lipase in this patient. This autosomal recessive condition may be allelic with Wolman disease with a more malignant course in this family than in most reported cases.
 ...
PMID:Cholesterol ester storage disease: clinical, biochemical, and pathological studies. 85 64

Acid lipase deficiency which is an inborn error of lipid metabolism leads to an abnormal accumulation of cholesteryl esters and triglycerides in many tissues. It is manifested in two clinical forms: Wolman's disease (WD) which is fatal in infancy and cholesteryl ester storage disease (CESD) which is a milder form and usually presented in adulthood. An infant with a clinical diagnosis of WD was examined with CT and ultrasound. Where as CT showed an enlarged liver with decreased density and heavily calcified adrenal glands, ultrasound revealed an enlarged liver with normal echogenicity, adrenal calcification and thickening of bowel loops. Bowel wall thickening in WD was not demonstrated in the literature before with any imaging modality.
 ...
PMID:Wolman's disease: ultrasonographic and computed tomographic findings. 149 19

Cholesterol ester storage disease (CESD) is infrequent in children. Four new cases in two nonrelated families are presented. Acid lipase deficiency in the leukocytes of the patients and reduced activity (50%) in those of parents were demonstrated. Clinical manifestations varied from neonatal cholestasis to asymptomatic hepatomegaly. Hepatic histology showed lipid vacuoles and cholesterol ester storage in hepatocytes and Kupffer cells. Increased levels of cholesterol and hepatomegaly were the first findings. There is as yet no specific treatment for CESD; however, the early detection of cases would make possible the timely control of complications.
 ...
PMID:Cholesterol ester storage disease: clinical, biochemical, and pathological studies of four new cases. 329 Apr 19

In newborn twins at three hours of age adrenal calcification has been detected. In addition to hepatomegaly, vomiting and diarrhoea, characteristic radiological findings confirmed the diagnosis of the rare heritable lipidosis, Wolman's disease.
 ...
PMID:Wolman disease in twins. 398 53

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.
 ...
PMID:Cholesteryl ester storage disease and Wolman disease: phenotypic variants of lysosomal acid cholesteryl ester hydrolase deficiency. 609 11

Acid lipase deficiency leads to the abnormal accumulation of cholesteryl esters and triglycerides in many tissues. It is manifested clinically in two forms: Wolman disease, which is usually fatal in infancy, and cholesteryl ester storage disease (CESD), which is clinically milder. One case of each is presented. In the patient with Wolman disease, computed tomography (CT) showed an enlarged liver of diminished density and enlarged adrenals with cortical calcification. Computed tomography of the patient with CESD showed an enlarged liver of normal density and normal adrenals. In vitro CT density is inversely related to cholesterol content. However, CT is unreliable in assessing liver cholesterol in these patients due to their poor nutrition and concomitant changes in liver glycogen and fat.
 ...
PMID:CT findings in acid lipase deficiency: wolman disease and cholesteryl ester storage disease. 688 32

A girl presented with small stature, obesity, tapetoretinal degeneration, deafness, psychomotor regression, seizures, acanthosis nigricans, hepatomegaly, and chronic tubulointerstitial nephropathy. She died at age ten with renal insufficiency and uncontrolled seizures. Histochemistry showed lipid storage in hepatocytes, histiocytes, smooth muscles and, to a much lesser extent, kidney tubules and cortical neurons. The liver had increased cholesterol esters (5-fold) and triacylglycerols (8-fold), and decreased phospholipids (50%). Methyllumbelliferyl-oleate, oleylcholestrol, trioleylglycerol, and tripalmitylglycerol lipase activities were markedly reduced in the liver, in the range found in Wolman's disease. In cirrhotic fatty livers these activities ranged from 7-87% of the normal mean. The patient's brain had limited neutral lipid storage and normal methyllumbelliferyl-oleate lipase. Trioleylglycerol lipase activity was 14-60% of controls; tripalmitylglycerol lipase activity 14-25% of controls; and oleylcholestrol lipase activity 12-33% of controls.
 ...
PMID:Neutral lipid storage with acid lipase deficiency: a new variant of Wolman's disease with features of the Senior syndrome. 715 65

Wolman disease and cholesteryl ester storage disease (CESD) are caused by a deficiency of lysosomal acid lipase activity, resulting in massive accumulation of cholesteryl ester and triglycerides. Wolman disease occurs in infancy, with hepatosplenomegaly, steatorrhea and adrenal calcification. It is fatal before the age of 1 year. In CESD, hepatomegaly may be the only clinical abnormality, although lipid deposition is widespread. Lysosomal acid lipase hydrolyzes both triaclyglycerols and cholesteryl esters, and the enzyme plays an important role in the cellular processing of plasma lipoproteins, and contributes to homeostatic control of lipoprotein levels in blood and prevention of cellular lipid overloading. The gene encoding lysosomal acid lipase was cloned and characterized in 1994, and two mutations of acid lipase gene were found in a patient with Wolman disease, as a compound heterozygote. It is suggested that structural gene defects are also present in CESD cells. However, the reason (s) for the clinical difference between Wolman disease and CESD remain (s) to be studied.
 ...
PMID:[Acid lipase deficiency: Wolman disease and cholesteryl ester storage disease]. 857 49

Lysosomal acid lipase (LAL) deficiency leads to two phenotypically different diseases: cholesteryl ester storage disease (CESD) and Wolman's disease. Lysosomal acid lipase hydrolyzes cholesteryl esters and triglycerides. Deficiency of LAL results in intralysosomal storage of cholesteryl esters and triglycerides. CESD has a chronic and benign course and is characterized by hepatomegaly and mild hypercholesterolemia. It leads to fibrosis (cirrhosis) and early atherosclerosis. This report presents the clinical, biochemical and microscopic data of seven patients with CESD followed up over 10 years. The physical development of all the study children remained within the normal range; 7 patients had hepatomegaly and 6 also had splenomegaly. Three patients had normal cholesterol, triglycerides and transaminases values; the other four had slightly elevated levels for these parameters. The activity of LAL in all patients was reduced to below 30% of the lower normal value. Histologically, cholesteryl crystals and lipid storage vacuoles in Kupffer cells were present in all examined patients except one. Accumulation of cholesteryl esters was visible on thin-layer chromatography of lipid extracts obtained from liver biopsies.
 ...
PMID:Clinical, biochemical and histological analysis of seven patients with cholesteryl ester storage disease. 944 50


1 2 3 4 Next >>