Analysis of myelin from a leukodystrophic brain was performed (Pelizaeus-Merzbacher disease, classical type). Myelin recovery was 7% of normal, when isolated by ultracentrifugation. Electron microscopy showed a great amount of loose lamellae, with less thick sheaths and periodicity close to normal. This myelin contains fewer lipids than normal, sphingolipids and plasmalogens being reduced. Fatty acids from phospholipids are essentially normal, however enols from plasmalogens are largely reduced. Purified sphingolipids (cerebrosides, sulfatides and sphingomyelin) present a considerable diminution in very long chain fatty acids; the ratio of very long chain fatty acids (over C I8) on shorter chains is 1% of the normal value for saturated fatty acids and 2% for the monounsaturated homologues. Protein analysis showed that basic protein and proteolipids were reduced, Wolfgram proteins being relatively increased.
Biochemical analysis of the leukodystrophic brain from a case of Pelizaeus-Merzbachcr disease, classical type. was performed. A decrease in the amount of solid material present was found. The lyophilized brain weight was reduced to 76% of normal with a slightly greater decrease in the amount of extractable lipid. Total myelin was diminished to 7% of normal. Among specific lipids plasmalogens were present in slightly lowered amounts. Cerebrosides and sulphatides were drastically reduced to 8% of normal. whereas sphingomyelin was less severely affected. Fatty acids from phospholipids were close to normal. only enols being slightly diminished. Analysis of pure cerebrosides and sulphatides revealed that the a-hydroxylated compounds as well as very long chain fatty acids (over CI8. especially C,, to CZ6) were greatly reduced. For chain lengths over C,,,, the ratio of leukodystrophic fatty acid to normal fatty acid was close to 10%. The defect in very long chain fatty acids is estimated at 99.204 in total brain. Thus, we have found a marked decrease in the amount of very long chain fatty acids and a less marked decrease in sphingolipids. The reduced amount of these acids appears to be partially oflsct by an increase in the amount of medium-chain fatty acids in sphingolipids. We conclude that one aspect of Pclizaeus-Mcrzbacher disease may be a defect in the synthesis of myelin very long chain fatty acids (as these acids are far much reduced than any other myelin molecule).
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