An adult case of adrenoleukodystrophy with features of olivo-ponto-cerebellar atrophy: II. Lipid biochemical studies.
Different portions with or without demyelination or degeneration of formalin-fixed brain tissues of a patient with adrenoleukodystrophy and a control subject were applied to analyses of lipids, particularly sphingolipids and cholesteryl ester. Demyelinated area of the white matter in the occipital lobe showed marked decrease in cerebroside and sulfatide except for sphingomyelin and, conversely an accumulation of cholesteryl ester, whereas un-demyelinated white matter in the frontal lobe showed no abnormalities in lipids. Abnormalities of lipids in degenerated lateral nuclei of the thalamus were not so remarkable as the demyelinated white matter, whereas apparently normal dorsomedial nuclei of the thalamus showed no abnormalities in lipids. With regard to the fatty acid composition of abnormal lipids in the demyelinated white matter, all sphingolipids of cerebroside, sulfatide, and sphingomyelin showed remarkable reduction of their longer chain fatty acids and, conversely a significant increment of shorter chain fatty acids. However, these fatty acids in the degenerated lateral nuclei of the thalamus were not so different from those in the undemyelinated and apparently normal areas as well as in control brain. The fatty acids of cholesteryl ester contained mainly C18:1 and C16 acids, and very long chain fatty acids, namely fatty acids with chain length more than 22 carbons, by about 22% of the total fatty acids. In view of the analytical results of the fatty acid composition of brain lipids, it was inconceivable that this ALD patient brain showed especially the accumulation of very long chain fatty acids, and that the biochemical defect in this disease was related to the abnormal oxidation of very long chain fatty acids in peroxisomes. However, the neuropathological findings of demyelination, reactive astrocytosis, and massive infiltration of foam cells well correlated with the abnormalities in myelin lipids and the accumulation of cholesteryl ester. Also, the lower values of urinary 17-ketosteroid and 17-hydroxycorticosteroid suggested that the failure of ACTH to stimulate corticoid secretion seemed to indicate the relationship between the adrenocortical insufficiency and the affected areas of the central nervous system.
D000326:Adrenoleukodystrophy / Q000378:metabolism*; D000328:Adult; D001921:Brain / Q000378:metabolism*; D002554:Cerebrosides / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D009849:Olivopontocerebellar Atrophies; D013107:Sphingolipids / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D013132:Spinocerebellar Degenerations; D013433:Sulfoglycosphingolipids / Q000378:metabolism
D002554:Cerebrosides; D002788:Cholesterol Esters; D005227:Fatty Acids; D013107:Sphingolipids; D013109:Sphingomyelins; D013433:Sulfoglycosphingolipids