Abstract
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 ∼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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Amirkhan RH, Timmons CF, Brown KO, Weinberger MJ, Bennett MJ (1997) Clinical, biochemical, and morphologic investigations of a case of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Arch Pathol Lab Med 121: 730-734.
Bennett MJ, Powell S (1994) Metabolic disease and sudden, unexpected death in infancy. Hum Pathol 25: 742-746.
Bennett MJ, Hale DE, Coates PM, Stanley CA (1991) Postmortem recognition of fatty acid oxidation disorders. Pediatr Pathol 11: 365-370.
Bennett MJ, Weinberger MJ, Kobori JA, Rinaldo P, Burlina AB (1996) Mitochondrial short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase deficiency: a new defect of fatty acid oxidation. Pediatr Res 39: 185-188.
Boles RG, Buck EA, Blitzer MG, et al (1998) Retrospective biochemical screening of fatty acid oxidation disorders in postmortem livers of 418 cases of sudden death in the first year of life. J Pediatr 132: 924-933.
Chalmers RA, Stanley CA, English N, Wigglesworth JS (1997) Mitochondrial carnitine-acylcarnitine translocase deficiency presenting as sudden neonatal death. J Pediatr 131: 220-225.
Cristofalo VJ, Allen RG, Pignolo RJ, Martin BG, Beck JC (1998) Relationship between donor age and the replicative lifespan of human cells in culture: a reevaluation. Proc Natl Acad Sci USA 95: 10614-10619.
Eaton S, Bartlett K, Pourfarzam M (1996) Mammalian mitochondrial beta-oxidation. Biochem J 320: 345-357.
He XY, Merz G, Mehta P, Schulz H, Yang S-Y (1999) Human brain short chain L-3-hydroxyacyl coenzyme A dehydrogenase is a single-domain multifunctional enzyme. Characterization of a novel1 7 beta-hydroxysteroid dehydrogenase. J Biol Chem 274: 15014-15019.
He XY, Yang YZ, Schulz H, Yang SY (2000) Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase. Biochem J 345: 139-143.
Rinaldo P, Stanley CA, Hsu BY, Sanchez LA, Stern HJ (1997) Sudden neonatal death in carnitine transporter deficiency. J Pediatr 131: 304-305.
Rinaldo P, Raymond K, al-Odaib A, Bennett MJ (1998) Clinical and biochemical features of fatty acid oxidation disorders. Curr Opin Pediatr 10: 615-621.
Rinaldo P, Yoon H-R, Yu C, Raymond K, Tiozzo C, Giordano G (1999) Sudden and unexpected death: a protocolf or the postmortem diagnosis of fatty acid oxidation disorders. Semin Perinatol 23: 204-210.
Saudubray J-M, Martin D, Poggi-Travert F, Billette de Villemeur T (1997) Clinical presentations of inherited mitochondrial fatty acid oxidation disorders: an update. Int Pediatr 12: 34-40.
Tein I, De Vivo DC, Hale DE, et al (1991) Short-chain L-3-hydroxyacyl-CoA dehydrogenase deficiency in muscle: a new cause for recurrent myoglobinuria and encephalopathy. Ann Neurol 30: 415-419.
Tyni T, Rapola J, Paetau A, Palotie A, Pihko H (1997) Pathology of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency caused by the G1528C mutation. Pediatr Pathol Lab Med 17: 427-447.
Vockley J (1994) The changing face of disorders of fatty acid oxidation. Mayo Clin Proc 69: 249-257.
Vredendaal PJCM, van den Berg IET, Stroobants AK, van der A DL, Malingre HEM, Berger R (1998) Structural organization of the human short-chain L-3-hydroxyacyl-CoA dehydrogenase gene. Mamm Genome 9: 763-768.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Renaud, D.L., Edwards, V., Wilson, G.J. et al. Glucose-free medium exacerbatesmicrovesicular steatosis in cultured skin fibroblasts of genetic defects of fatty acid oxidation. A novel screening test. J Inherit Metab Dis 25, 547–555 (2002). https://doi.org/10.1023/A:1022039206660
Issue Date:
DOI: https://doi.org/10.1023/A:1022039206660