title: Clinical variation in X-linked adrenoleukodystrophy: fatty acid and lipid metabolism in cultured fibroblasts.
abstract: To determine whether the clinical phenotype of ALD correlates with the extent of metabolic abnormality, we investigated VLFA metabolism in cultured fibroblasts from patients with the clinically severe childhood from of ALD and the milder AMN variant. No differences were seen in the content of neutral lipids or phospholipids, in incorporation of [1-14C]lignocerate into cellular lipids, or in the fatty acid composition of fibroblasts from patients with childhood ALD or AMN. [1-14C]Lignocerate oxidation was deficient to a similar extent (35-40% of normal) in both intact fibroblasts and cell homogenates from patients with childhood ALD and AMN. With the use of fibroblast homogenates, oxidation of lignocerate was partially inhibited by various long-chain fatty acids, and residual activity in ALD homogenates was more susceptible to inhibition by palmitate than normal. In the presence of competing palmitate, residual lignocerate oxidative activity in fibroblast homogenates was reduced to 20 +/- 4% of normal in childhood ALD and 24 +/- 2% of normal in AMN. These results indicate that residual VLFA oxidative activity, fatty acid composition, VLFA metabolism, and lipid content of cultured fibroblasts do not correlate with the clinical expression of the ALD gene.
authors.affiliation: Department of Human Genetics, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
authors.forename: D J
authors.initials: DJ
authors.lastname: Boles
authors.forename: D A
authors.initials: DA
authors.lastname: Craft
authors.forename: D A
authors.initials: DA
authors.lastname: Padgett
authors.forename: R M
authors.initials: RM
authors.lastname: Loria
authors.forename: W B
authors.initials: WB
authors.lastname: Rizzo
mesh_terms: D000326:Adrenoleukodystrophy / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D002478:Cells, Cultured; D002648:Child; D005227:Fatty Acids / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D008040:Genetic Linkage; D006801:Humans; D050356:Lipid Metabolism; D010084:Oxidation-Reduction; D014960:X Chromosome
chemical_list: D005227:Fatty Acids