Wolman disease and cholesteryl ester storage disease diagnosed by histological and ultrastructural examination of intestinal and liver biopsy

Boldrini, Renata; Vito, Rita De; Biselli, Roberto; Filocamo, Mirella; Bosman, Cesare

doi:10.1016/j.prp.2003.11.001

Cited by 64 publications

(51 citation statements)

References 12 publications

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“…Affected WD infants display massive accumulations of CEs and TGs in macrophages throughout the viscera. CE and TG accumulations in liver and lung can lead to liver cirrhosis and pulmonary fibrosis (4,5). Excess CEs in the zona reticularis of the adrenal gland lead to adrenal calcification and insufficiency (2,6).…”

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confidence: 99%

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Wolman disease/cholesteryl ester storage disease: efficacy of plant-produced human lysosomal acid lipase in mice

Cameron²,

Garger

et al. 2008

Journal of Lipid Research

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confidence: 99%

“…Excess CEs in the zona reticularis of the adrenal gland lead to adrenal calcification and insufficiency (2,6). WD patients develop cachexia from malabsorption related to the accumulation of engorged macrophages in the villi of the small intestine (2,4). The mean life span for patients with WD is ?6 months.…”

mentioning

confidence: 99%

Wolman disease/cholesteryl ester storage disease: efficacy of plant-produced human lysosomal acid lipase in mice

Cameron²,

Garger

et al. 2008

Journal of Lipid Research

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“…6 Subsequent studies indicated TG hydrolysis is exclusively achieved via lysosomal acid lipase, which is encoded by the Lipa gene. The importance of lysosomes in TG hydrolysis is underscored by the excessive lipid accumulation in liver of patients that carry a mutation in the LIPA gene, 7 and in Lipa knockout mice. 8 However, it was never fully clear how lipid droplets actually end up in lysosomes.…”

Section: Commentmentioning

confidence: 99%

“…6 Other risks associated with development of cirrhosis or hepatocellular carcinoma include HBV genotype C and F infection, HBV DNA levels Ͼ2000 IU/mL, and basal core promoter mutations. 7 To date, several genetic variants have been found to have an association with chronic HBV infection, including interferon-␥, tumor necrosis factor, 8 vitamin D receptor, 9 estrogen receptor 1, 10 and several human leukocyte antigen (HLA) loci. [11][12][13][14] However, some studies have yielded conflicting results.…”

Section: Commentmentioning

confidence: 99%

Dropping liver fat droplets†

Kersten

Müller

2009

Hepatology

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The intracellular storage and utilization of lipids are critical to maintain cellular energy homeostasis. During nutrient deprivation, cellular lipids stored as triglycerides in lipid droplets are hydrolysed into fatty acids for energy. A second cellular response to starvation is the induction of autophagy, which delivers intracellular proteins and organelles sequestered in double-membrane vesicle (autophagosomes) to lysosomes for degradation and use as an energy source. Lipolysis and autophagy share similarities in regulation and function but are not known to be interrelated. Here we show a previously unknown function for autophagy in regulating intracellular lipid stores (macrolipophagy). Lipid droplets and autophagic components associated during nutrient deprivation, and inhibition of autophagy in cultured hepatocytes and mouse liver increased triglyceride storage in lipid droplets. This study identifies a critical function for autophagy in lipid metabolism that could have important implications for human diseases with lipid over-accumulation such as those that comprise the metabolic syndrome. CommentThe liver plays an important role in the regulation of fat metabolism. During feeding and fasting, the liver actively takes up fat in the form of triglyceride (TG)-containing remnant particles and circulating free fatty acids. Furthermore, the liver synthesizes fatty acids from glucose via de novo lipogenesis. The incoming fatty acids are either partially or completely oxidized or are converted into TGs, which can be exported into the bloodstream in the form of very low density lipoprotein particles. Under conditions when excess hepatic uptake of fatty acids cannot be properly compensated for by increased fatty acid breakdown or increased TG secretion, fatty liver or steatosis ensues. Fatty liver is characterized by the presence of numerous lipid droplets dispersed throughout the cytoplasm of parenchymal cells. This abnormal fat storage represents the early stage of nonalcoholic fatty liver disease (NAFLD), which is the most common liver pathology in Western countries and is considered the hepatic manifestation of the metabolic syndrome. For reasons that are still not fully understood in certain individuals, the hepatic steatosis progresses toward the more severe nonalcoholic steatohepatitis (NASH), which could eventually lead to cirrhosis, liver failure, and even hepatocellular carcinoma.Although fluctuations in TG levels are a normal response to changes in nutritional status, chronically elevated hepatic lipid storage clearly represents a pathological phenomenon. Elevated TG stores can also be actively dissipated, for example by agonists of the peroxisome proliferator-activated receptor alpha (PPAR␣), which stimulate oxidation of fatty acids in mitochondria and peroxisomes. Conversely, inhibition of fatty acid oxidation leads to pronounced steatosis. 1,2 Although the process of fatty acid oxidation has been extensively studied, much less is known about TG hydrolysis and the breakdown of lipid droplets.I...

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“…Kupffer cells are histologic indicators, which are seen in a field of swollen hepatocytes with micro vesicular steatosis. Lipid accumulation in hepatocytes causes histologic changes, such as fibrosis and cirrhosis (6,7). Therefore, impaired liver function tests, such as increase in serum transaminases, alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) are expected (8).…”

Section: Introductionmentioning

confidence: 99%

Histopathological Findings in Cholesteryl Ester Storage Disease: A Report of Three Cases

et al. 2017

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Cholesteryl ester storage disease (CESD) is a disorder in which cholesteryl esters (CE) and triglycerides (TG) are preserved particularly in hepatocytes. The exact clinical manifestation is not known due to a lack of sufficient data. The current study presents 3 new cases of CESD with 2 of them being siblings. All had perturbed serum low-density lipoprotein (LDL), lactate dehydrogenase (LDH), triglyceride, and cholesterol. Hepatosplenomegaly was seen in all the patients. Liver biopsy showed fat storage in hepatocytes. Adrenomegaly or adrenal calcification, portal hypertension, esophageal varices, and hepatic scarring were not observed in any of the patients. Histopathologic features of CESD, including fat storage in hepatocytes, could characterize these patients.

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Wolman disease and cholesteryl ester storage disease diagnosed by histological and ultrastructural examination of intestinal and liver biopsy

Cited by 64 publications

References 12 publications

Wolman disease/cholesteryl ester storage disease: efficacy of plant-produced human lysosomal acid lipase in mice

Wolman disease/cholesteryl ester storage disease: efficacy of plant-produced human lysosomal acid lipase in mice

Dropping liver fat droplets†

Histopathological Findings in Cholesteryl Ester Storage Disease: A Report of Three Cases

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