linoleic-acid and Adrenoleukodystrophy

Topics: Acyl-CoA Oxidase; Adolescent; Adrenoleukodystrophy; Adult; alpha-Tocopherol; Animals; Apoptosis; ATP-Binding Cassette Transporters; Brain; Case-Control Studies; Catalase; Cell Survival; Child; Disease Progression; Docosahexaenoic Acids; Glutathione; Humans; Hydrogen Peroxide; Ketocholesterols; Linoleic Acid; Male; Membrane Proteins; Mice; Microglia; Middle Aged; Oxidative Stress; Peroxisomes; Reactive Oxygen Species; Repressor Proteins; Young Adult

Blood cell and plasma lipid classes and their fatty acids were analyzed in a child with X-linked adrenoleukodystrophy. The increase in saturated fatty acids with very long chains typical of this disease occurred almost exclusively in sphingomyelin. In this lipid, the proportion of lignoceric (24:0) and hexacosanoic (26:0) acids increased while that of 18:0, 20:0, and 24:1 decreased. In the rest of the lipid classes, but especially in cholesteryl esters and triacylglycerols, the proportion of linoleate (18:2) decreased while that of oleate (18:1) increased. In glycerophospholipids, polyunsaturated fatty acids such as 20:4n-6, 22:5n-6, and 22:6n-3 were reduced while their immediate precursors, 20:3n-6, 22:4n-6, and 22:5n-3, respectively, were relatively increased, suggesting a defect in fatty acid desaturation mechanisms. Although less pronounced, a similar trend of changes was seen in the patient's mother; in both, all alterations were more marked in serum than in blood cells.

Topics: Adrenoleukodystrophy; Child; Fatty Acids; Fatty Acids, Unsaturated; Genetic Linkage; Humans; Linoleic Acid; Linoleic Acids; Male; Oleic Acid; Oleic Acids; Phospholipids; Sphingomyelins; X Chromosome

The purpose of the study was to compare the polyunsaturated fatty acid (PUFA) status in patients with X-linked adrenoleukodystrophy or adrenomyeloneuropathy (X-ALD/AMN) with that in disorders of peroxisome biogenesis (PB). Total fatty acids and plasmalogens were quantified in plasma and red cells from 28 patients with X-ALD/AMN, 26 patients with generalized peroxisomal disorders, and 37 controls. Total fatty acid methyl esters and plasmalogen dimethyl acetals were obtained by direct transmethylation and separated by capillary column gas chromatography. The results confirm previous findings in that docosahexaenoic acid (DHA, 22:6n-3) was greatly decreased in both plasma and erythrocytes from patients with PB disorders. When nutritional conditions were adequate, patients with X-ALD/AMN had normal levels of DHA. A highly significant positive correlation was found between the levels of DHA and those of plasmalogens in peroxisomal patients. As in other tissues, the parent n-6 fatty acid, linoleic acid (LA, 18:2n-6) was significantly increased in red cells from PB patients, whereas arachidonic acid (20:4n-6) was virtually within normal limits. In clear contrast to red cells and other tissues, arachidonate was significantly lower in plasma from PB patients. The decrease in plasma arachidonate and the high tissue levels of LA suggest a defect of delta 6 desaturase and/or delta 5 desaturase in PB patients. The n-6 fatty acids were normal in X-ALD/AMN patients. The present data show that X-ALD/AMN patients do not have the profound PUFA alterations that PB patients have, at least in blood.

Topics: Adolescent; Adrenoleukodystrophy; Adult; Arachidonic Acid; Child; Child, Preschool; Docosahexaenoic Acids; Erythrocytes; Fatty Acids, Unsaturated; Humans; Infant; Linoleic Acid; Linoleic Acids; Metabolism, Inborn Errors; Methylation; Microbodies; Plasmalogens; X Chromosome