Glucose-free medium exacerbates microvesicular steatosis in cultured skin fibroblasts of genetic defects of fatty acid oxidation. A novel screening test.
Skin fibroblasts from patients with various fatty acid oxidation defects (FAOD) and four normal controls were subcultured in standard glucose-containing medium or in glucose-free medium simulating fasting. The FAOD fibroblasts developed microvesicular steatosis, which was greatly exacerbated in glucose-free medium. 'Rescue treatment' with glucose-containing medium was performed in the short-chain L-3-hydroxyacyl-CoA dehydrogenase-deficient (SCHADD) fibroblasts and resulted in a partial resolution of the steatosis and improved cellular viability. Transmission electron microscopy of autopsy specimens from the SCHADD patient demonstrated that most renal interstitial fibroblasts and approximately 50% of fibroblasts in the heart had microvesicular steatosis. The demonstration of microvesicular steatosis in parenchymal and/or cultured skin fibroblasts may provide important and cost-effective screening tools for the detection of genetic defects of fatty acid oxidation.
Renaud
D L
DL
Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Edwards
V
V
Wilson
G J
GJ
Tein
I
I
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D002478:Cells, Cultured; D003470:Culture Media; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005947:Glucose; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology; D008854:Microscopy, Electron; D010084:Oxidation-Reduction; D012867:Skin / Q000378:metabolism / Q000473:pathology
D003470:Culture Media; D005227:Fatty Acids; D015094:3-Hydroxyacyl CoA Dehydrogenases; D005947:Glucose