Disease relevance of Wolman Disease

• Cholesteryl ester storage disease and Wolman disease: phenotypic variants of lysosomal acid cholesteryl ester hydrolase deficiency [1].
• Wolman disease is a lethal lysosomal storage disease due to deficiency of lysosomal acid lipase (LAL) [2].

High impact information on Wolman Disease

• LAL defects cause Wolman disease (WD) and CE storage disease (CESD) [3].
• CRM specific activity toward triolein and cholesteryl oleate was reduced about 200-fold in the Wolman disease fibroblasts and 50- to 100-fold in the cholesterol ester storage disease cells when compared to normal [4].
• Deficiency of LAL in humans leads to Wolman disease and cholesteryl ester storage disease that result, respectively, in the intralysosomal storage of both neutral lipids or only cholesteryl esters [5].
• We previously reported a rat model of Wolman's disease (Wolman rat) that is deficient for LAL activity [6].
• In contrast, when PMLes dissolved in 2% dimethyl sulphoxide was added directly to the culture medium, its hydrolysis was similar in lymphoblastoid cells from controls and from patients affected with Wolman disease, neutral lipid storage disease or familial hypercholesterolaemia [7].

Chemical compound and disease context of Wolman Disease

• Acid lipase cross-reacting material in Wolman disease and cholesterol ester storage disease [4].
• Accumulation of glyceryl ether lipids in Wolman's disease [8].
• The sources and the catabolic pathways of cytoplasmic pools of triacylglycerols and cholesteryl esters have been comparatively investigated in cultured fibroblasts from normal subjects and from patients affected with neutral lipid storage disease (NLSD) and Wolman disease (WD) [9].
• Wolman's disease cells hydrolyzed CL at 10-22% and triolein at 11-19% the rate of normal cells; cholesterol ester storage disease cells hydrolyzed these substrates at 28-49 and 30-47% the normal rate, respectively [10].
• The experiments reported here allowed us to compare the metabolism of neutral lipids from extracellular origin (lipoproteins) and endogenous origin (triacylglycerol biosynthesis induced by feeding cells with high levels of free fatty acid) in normal and acid-lipase-deficient fibroblasts (Wolman's disease) [11].

Biological context of Wolman Disease

• In order to elucidate the underlying molecular defects in Wolman disease, we have characterized the hLAL gene in two female Wolman patients of German and Turkish origin by SSCP and DNA sequence analysis [12].

Anatomical context of Wolman Disease

• We investigated the pathological and biochemical changes of skeletal muscle in rats with lysosomal acid lipase deficiency, which is an animal counterpart of human Wolman's disease [13].
• Thus, this similar deficiency demonstrates that, in lymphoid cell lines, triolein and cholesteryl esters are hydrolysed (under the conditions used here) by a single enzyme, i.e., lysosomal acid lipase muted in Wolman's disease [14].

Gene context of Wolman Disease

• A new mutation (LIPA Tyr22X) of lysosomal acid lipase gene in a Japanese patient with Wolman disease [15].
• The hypoxia-induced group further included the genes for Niemann-Pick C disease and for Wolman disease [lysosomal acid lipase (LAL)] [16].
• Enzyme studies on Epstein-Barr virus-transformed lymphoid cell lines from Wolman's disease. Lipases, cholesterol esterase and 4-methylumbelliferyl acyl ester hydrolases [14].

Analytical, diagnostic and therapeutic context of Wolman Disease

• Normal fluorine-18-labelled 2-fluoro-2-deoxyglucose positron emission tomography and magnetic resonance imaging of the brain in Wolman disease [17].

References