Summary
Neutral lipid storage disease with ichthyosis is a newly recognized heritable disorder characterized by widespread cellular triglyceride storage. Lipid metabolism in fibroblasts cultured from three affected family members was studied. The stored lipid is triglyceride composed of an unremarkable fatty acid profile and derived from both exogenously-supplied and endogenously-synthesized fatty acids. Lipid storage could not be corrected by prolonged culture in lipid-depleted media. Acetyl CoA carboxylase activity and β-oxidation of palmitate were both normal. Taken together, these studies exclude a primary defect of fatty acid uptake, over-synthesis or impaired β-oxidation. Moreover, triacylglycerol lipase activity of homogenates of fibroblasts from patients with NLSDI examined over the range of pH 3.5–8.5 was normal.
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References
Angelini, C., Philippart, M., Borrone, C., Bresolin, N., Cantini, M. and Lucke, S. Multisystem triglyceride storage disorder with impaired long-chain fatty acid oxidation.Ann. Neurol. 7 (1980) 5–10
Bell, R. M. and Coleman, R. A. Enzymes of glycerolipid synthesis in eukaryzotes.Ann. Rev. Biochem. 49 (1980) 459–487
Brown, B. E., Williams, M. L. and Elias, P. M. Stratum corneum lipid abnormalities in ichthyosis: detection by a new lipid microanalytical method.Arch. Dermatol. 120 (1984) 204–209
Cham, B. E. and Knowles, B. R. A solvent system for delipidation of plasma or serum without protein precipitation.J. Lipid Res. 17 (1976) 176–181
Chanarin, I., Patel, A., Slavin, G., Wills, E. J., Andrews, T. M. and Stewart, G. Neutral lipid storage disease: a new disorder of lipid metabolism.Br. Med. J. 1 (1975) 553–555
Dorfman, M. L., Hershko, C. and Eisenberg, S. Ichthyosiform dermatosis with systematic lipidosis.Arch. Dermatol. 110 (1974) 261–266
Elias, P. M., Brown, B. E., Fritsch, P. O., Goerke, R. J., Gray, G. M. and White, R. J. Localization and composition of lipids in neonatal mouse stratum granulosum and stratum corneum.J. Invest. Dermatol. 73 (1979) 339–348
Elias, P. M. and Williams, M. L. Neutral lipid storage disease with ichthyosis: defective lamellar body contents and intercellular dispersion.Arch. Dermatol. 121 (1985) 1000–1008
Elsbach, P. and Farrow, S. Cellular triglyceride as a source of fatty acid for lecithin synthesis during phagocytosis.Biochim. Biophys. Acta 176 (1969) 438–441
Gonzales-Rios, M. C., Whitney, S. C., Williams, M. L., Elias, P. M. and Packman, S. Lipid metabolism in biotin-responsive multiple carboxylase deficiency.J. Inher. Metab. Dis. 8 (1985) 184–186
Havel, R. J., Eder, H. and Bragdon, J. Distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum.J. Clin. Invest. 34 (1955) 1345–1350
Hubscher, G. Glyceride metabolism. In Salik, J. and Wakil (eds.)Lipid Metabolism. Academic Press, 1970, pp. 279–370
Kramer, J. K. G., Farnworth, E. R. and Thompson, B. K. Quantitating heart lipids: comparison of results obtained using the Iatroscan method with those from phosphorus and gas chromatographic techniques.Lipids 20 (1985) 536–541
Labaraca, C. and Poigen, P. A simple rapid, and sensitive DNA assay procedure.Anal. Biochem. 102 (1980) 344–352
Maltese, W. A., Reitz, B. A. and Volpe, J. J. Changes in synthesis of sterols and fatty acids associated with inhibition of growth of L-M cells at high cell density.Biochim. Biophys. Acta 663 (1981) 645–652
Miranda, A., DiMauro, S., Eastwood, A., Hays, A., Johnson, W. G., Olarte, M., Whitlock, R., Mayeux, R. and Rowland, L. P. Lipid storage, myopathy, ichthyosis and steatorrhea.Muscle Nerve 2 (1979) 1–13
Oram, J. F., Shafrin, E. and Bierman, E. L. Triacylglycerol metabolism and triacylglycerol lipase activities of cultured human skin fibroblasts.Biochim. Biophys. Acta 619 (1980) 214–227
Rao, G. A., Riley, D. E. and Larkin, E. C. Comparison of the thin layer chromatography/flame ionization detection system with other methods for the quantitative analysis of liver lipid contents in alcohol-fed rats and controls.Lipids 20 (1985) 531–535
Rodbell, M. Metabolism of isolated fat cell. I. Effect of hormones on glucose metabolism and lipolysis.J. Biol. Chem. 239 (1964) 375–380
Slavin, G., Wills, E. J., Richmond, J. E., Chanarin, L., Andrews, T. and Stewart, G. Morphological features in a neutral lipid storage disease.J. Clin. Pathol. 28 (1975) 701–710
Smith, R. K., Krohn, R. I., Hermarson, G. I., Mallia, A. K., Gartner, F. H., Proverzan, M. D., Fujimoto, E. K., Goete, N. M., Olson, B. J. and Klenk, D. C. Measurement of proteins using bicinchoninic acid.Anal. Biochem. 150 (1985) 76–85
Spector, A. A., Mathur, S. N., Kaduce, T. L. and Hyman, B. T. Lipid nutrition and metabolism of cultured mammalian cells.Prog. Lipid. Res. 19 (1981) 155–186
Steinberg, D. Phytanic acid storage disease: Refsum's syndrome. In: Stanbury, J. B., Wyngaarden, J. B., Frederickson, D. S., Goldstein, J. L. and Brown, M. S. (eds.)The Metabolic Basis of Inherited Disease, McGraw-Hill, New York, 1983, pp. 731–747
Williams, M. L., Hughes-Fulford, M. and Elias, P. M. Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and sterol biosynthesis by cholesterol sulfate in cultured fibroblasts.Biochim. Biophys. Acta 845 (1985a) 349–357
Williams, M. L., Koch, T. K., O'Donnell, J. J., Frost, P., Epstein, L. B., Grizzard, W. S. and Epstein, C. H. Ichthyosis and neutral lipid storage disease.Am. J. Med. Genet 20 (1985b) 711–726
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Williams, M.L., Monger, D.J., Rutherford, S.L. et al. Neutral lipid storage disease with ichthyosis: Lipid content and metabolism of fibroblasts. J Inherit Metab Dis 11, 131–143 (1988). https://doi.org/10.1007/BF01799862
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DOI: https://doi.org/10.1007/BF01799862