Lipid composition of the nervous system in Refsum's disease

Abstract

The compositions of the major lipids and their constituent fatty acids and fatty aldehydes from cerebral gray matter, white matter, and myelin, spinal cord myelin, and sciatic nerve were determined in a 57 yr old woman who died of Refsum's disease. There were deficiencies of ethanolamine glycerophosphatides (EGP) in gray matter and frontal lobe myelin, and a lipid with the chromatographic properties of lyso-EGP accumulated in all tissues. The proportions of the remaining lipids were nearly normal in the central nervous system tissues. In the sciatic nerve the proportions of sphingolipids were small; this observation is consistent with the severe demyelination noted on pathologic examination. Cholesteryl esters were not detected in any tissue. Phytanate (3,7,11,15-tetramethylhexadecanoate) was present in the glycerophosphatides from each tissue. Higher proportions of phytanate were found in choline glycerophosphatides (CGP) than in EGP or in serine glycerophosphatides (SGP). Hydrolysis with phospholipase established that phytanate was confined to the 1-position of CGP. More phytanate was found in CGP from myelin than from gray or white matter. Fourfold higher proportions of phytanate were found in CGP from sciatic nerve than in CGP from the central nervous system: in sciatic nerve, 24% of the fatty acids of CGP consisted of phytanate. The proportions and compositions of sphingolipid hydroxy fatty acids and odd-numbered fatty acids were normal in each tissue. These findings argue against a defect in sphingolipid alpha-hydroxy acid metabolism in Refsum's disease. The results are consistent with the view that the accumulation of phytanate is responsible for the demyelination.