Progressive accumulation of toxic metabolite in a genetic leukodystrophy

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Science  18 May 1984:
Vol. 224, Issue 4650, pp. 753-755
DOI: 10.1126/science.6719111


Progressive accumulation of a cytotoxic metabolite, galactosylsphingosine (psychosine), was found in the brain of the twitcher mouse, a mutant caused by genetic deficiency of galactosylceramidase. Similar abnormal accumulation was also found in the brain of the genetic galactosylceramidase deficiency disease in the dog and in human patients (globoid cell leukodystrophy or Krabbe disease). Galactosylphingosine was absent in the brains of normal and heterozygous mice. The finding provides support for the psychosine hypothesis as the biochemical pathogenetic mechanism of globoid cell leukodystrophy. Analogous mechanisms may be important in the pathogenesis of other genetic lysosomal diseases.