The correlation between biochemical and histopathological findings in adrenoleukodystrophy.

Nine areas of the brain from a case of adrenoleukodystrophy were examined histopathologically and by gas chromatography for fatty acid content. The main findings were: (1) the degree of demyelination was related to the pentacosanoic and hexacosanoic to docosanoic acid ratios (C25:0/C22:0 and C26:0/C22:0); gliosis was related to the ratios of several fatty acids to docosanoic acid; (2) there was a shift towards smaller components (C22:0, C23:0, C24:0) of the saturated fatty acid series in the less affected areas, to larger components and various minor components in regions of active demyelination; (3) mainly saturated fatty acids of the middle class components (C24:0, C25:0 and C26:0) were found in severely affected areas where the active process is complete. Because a region of high long chain fatty acid content, lacking histopathological change, was detected, the hypothesis is presented that the primary event in childhood ALD is related to defective lipid metabolism and that this preceeds demyelination.