Cholesterol metabolism in cultured fibroblasts in adrenoleukodystrophy

Abstract

The basic biochemical defect of X-linked adrenoleukodystrophy (sudanophilic leukodystrophy, Schilder’s disease) is unknown. To investigate reported abnormalities in cholesterol metabolism in vitro, we examined cultured skin fibroblasts of four patients and four normal control subjects. The kinetics of retention and accumulation of [MC]cholesterol by these cells was studied. After 3 days of exposure to tracer amounts of [14C]cholesterol, an apparent steady state between the medium and cellular cholesterol was established. The specific radioactivity expressed per mg of protein was similar for both Schilder and control fibroblasts. After labeling the pre-existing cellular cholesterol pool, the rate of loss of label was followed up for a 6-day period. About 23% and 14%, respectively, of the cellular radioactivity in both Schilder’s disease and control cells were released into the medium after the consecutive change with fresh nonlabeled medium. No significant differences in [14C] cholesterol rates of uptake or release were observed between control and Schilder’s disease fibroblasts. About 44% of the labeled cholesterol was present in an esterfied form after incubation in the presence of unheated serum in both Schilder’s and control cultures. These results do not confirm previously reported abnormalities in cholesterol metabolism in cultured fibroblasts. Nevertheless, accumulating evidence from studies of fatty acid composition of brain and adrenal tissues in Schilder’s disease indicates the presence of an abnormal series of long chain fatty acids. Studies are now in progress to determine whether these possibly unique long chain fatty acids are evident in fibroblasts from patients with Schilder’s disease. © 1976 International Pediatric Research Foundation, Inc.