Sjogren-Larsson syndrome: accumulation of free fatty alcohols in cultured fibroblasts and plasma

Sjogren-Larsson syndrome (SLS) is an inherited disorder associated with def icient oxidation of long-chain aliphatic alcohols. Previous studies have re ported modest elevations in total (free + esterified) fatty alcohols in SLS , but free fatty alcohols have not been selectively measured, in part becau se of their low concentrations in most tissues and the presence of trace fa tty alcohol contaminants in some solvents used for their analysis. We adapt ed methods to measure free fatty alcohols in cultured cells and plasma that minimize exogenous alcohol contamination. Fatty alcohols were analyzed as acetate derivatives, using capillary column gas chromatography. By this met hod, cultured skin fibroblasts from SLS patients were found to have 7- and 8-fold elevations in the mean content of hexadecanol (16:0-OH) and octadeca nol (18:0-OH), respectively. The mean plasma 16:0-OH and 18:0-OH concentrat ions in SLS patients (n = 11) were 9- and 22-fold higher than in normal con trols, respectively. In SLS fibroblasts, most of the fatty alcohol (59%) th at accumulated was free rather than esterified alcohol, whereas free alcoho l accounted for 23% of the total alcohol in normal cells. These results ind icate that elevations in free fatty alcohols provide a sensitive marker for the enzymatic defect in SLS. The ability to measure free fatty alcohols in cultured cells and plasma should prove useful for investigations of normal fatty alcohol metabolism and the deranged metabolism in SLS.