Schilder’s disease: Abnormal cholesterol retention and accumulation in cultivated fibroblasts

Schilder’s disease (SD) with adrenal insufficiency is a fatal X-linked recessive disorder for which the basic defect is as yet unknown. To investigate the hypothesis that Schilder’s disease might be associated with a generalized defect in cholesterol metabolism, the uptake and disappearance of labeled cholesterol and cholesterol esters were studied in cultivated fibroblasts from patients with Schilder’s disease, patients with familial hypercholesterolemia, and normal control subjects. Over a 10–12-day period of exposure to the labeled compound, SD fibroblasts accumulated significantly more cholesterol than did normal fibroblasts (P < 0.001). In addition, after a 24-hr exposure to the labeled cholesterol, the SD fibroblasts retained significantly more of the label than did control cells over a 5-day period of study (P < 0.001). The retained label was still located in the cholesterol fraction on thin layer chromatography in both SD and normal cells. The total cholesterol content of SD cells when measured directly after 12 days in tissue culture was significantly greater than that of normal cells. The results of these studies support the concept that Schilder's disease may indeed be related to a generalized defect in cholesterol metabolism or transport. An alternative explanation for these findings is that Schilder's disease may be associated with a defect in membrane structure or turnover that is not directly related to cholesterol metabolism but can be followed in vitro by cholesterol accumulation and retention.