Molecular composition of the major glycolipids in globoid cell leukodystrophy

Abstract

Chemical studies were performed on the formalinized brain of an infant dying at 20 months of age of globoid cell leukodystrophy. The total lipid content was diminished in both specimens of white matter examined. The cerebrosldeisulfatide ratios were 2.8 in gray matter and 3.0 and 4.5 in 2 samples of white matter, as contrasted with a normal value of 2.4. Purified cerebrosides and sulfatides were prepared by successive Florisil, diethylaminoethanol cellulose, and silica column chromatography. Except for a reversal of the relative amounts of 24:0 and 24:1 fatty acids, a nonspecific abnormality, the structure of gray matter cerebrosides and of gray and white matter sulfatides was normal. In both samples of white matter cerebrosides, there was a relative lack of hydroxy fatty acids. In the specimen derived from parietal white matter, a striking loss of 24:0 and 24:1 non-hydroxy fatty acids was also observed. The sphingosine bases were normal in all fractions. Cerebrosides and sulfatides accounted for only 9% of total lipid hexose of gray matter and 18 and 34% in the 2 specimens of white matter. The remaining glycolipids consisted of ceramide dihexoside, ceramide trihexostde, and 2 other, still unidentified glycolipids, all present in relatively increased amounts. Ceramide dihexoside was isolated and found to consist of approximately equal amounts of glucose and galactose. The relationship of this substance whose immunogenic properties have been previously established, to the formation of globoid cells remains to be elucidated.