Abstract
Incorporation of acetate into digitonin precipitable fraction (DPF), fatty acid fraction (FAF) and CO2 were measured in monolayers of cultured skin fibroblasts from 4 homozygotes (HH) for familial hypercholesterolemia(FH), 6 heterozygotes (Hh), 10 controls (hh) and 4 subjects with type 4 and 5 hyperlipidemia. In cells preincubated for 20 hours in lipid free medium, counts per min per mg of protein (CpMp) in DPF were: HH, 19,600; hh, 20,700. In cells preincubated in standard medium with cholesterol (C) concentration of 3.5 mg%, CpMp were (mean ± SD): HH 3868 ± 2356; Hh, 725 ± 160; hh, 177 ± 79; type 4-5 hyperlipidemia, 168 ± 91. Counts in FAF and CO2 were similar in the 4 groups. Variation in time of incubation (30 to 240 min) and acetate concentration (0.03 to 1 μmole per flask) had no effect on direction or magnitude of differences. Increasing C in preincubation medium to 50 mg% did not suppress further the counts in HH. Results are in agreement with findings in liver slices (Lancet II, 778, 1969) and add further support to the hypothesis that the metabolic defect in FH is a derangement of the feedback inhibition of C synthesis. Fibroblast assay could be a useful tool for the etiological diagnosis of hyperlipidemia.
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Khachadurian, A., Lipson, M., Kawahara, F. et al. DIAGNOSIS OF FAMILIAL HYPERCHOLESTEROLEMIA BY MEASUREMENT OF CHOLESTEROL SYNTHESIS IN SKIN FIBROBLASTS. Pediatr Res 8, 434 (1974). https://doi.org/10.1203/00006450-197404000-00564
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DOI: https://doi.org/10.1203/00006450-197404000-00564