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Cholesterol ester storage disease and Wolman disease are recessive autosomal disorders caused by a deficiency in lysosomal acid lipase (LAL), also known as cholesteryl ester hydrolase.1,2 4-Methylumbelliferyl palmitate (4-MUP) is a fluorogenic substrate for lysosomal acid lypase (LAL).3 4-MUP is cleaved by LAL to release the fluorescent moiety 4-MU. 4-MU fluorescence is pH-dependent with excitation maxima of 320 and 360 nm at low (1.97-6.72) and high (7.12-10.3) pH, respectively, and an emission maximum ranging from 445 to 455 nM, increasing as pH decreases.4 4-MUP may also be cleaved by other acid lipases.5,6 Recent advances allow the assessment of LAL activity in very small blood volumes using 4-MUP.1,2
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1. A practical fluorometric assay method to measure lysosomal acid lipase activity in dried blood spots for the screening of cholesteryl ester storage disease and Wolman disease. Mol. Genet. Metab. 111(2), 193-196 (2014).
2. A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2. Clin. Chim. Acta 413(15-16), 1207-1210 (2012).
3. Fluorimetric assay of acid lipase in human leukocytes. Clin. Chim. Acta 97(2-3), 239-242 (1979).
4. Fluorescent properties of hymecromone and fluorimetric analysis of hymecromone in compound dantong capsule. J. Spectrosc. 147128 (2013).
5. Separation and characterization of the acid lipase and neutral esterases from human liver. Am. J. Hum. Genet. 32(6), 869-879 (1980).
6. Geotrichum candidum NRRL Y-