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Science 18 May 1984:
Vol. 224. no. 4650, pp. 753 - 755
DOI: 10.1126/science.6719111
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Articles

Science, Vol 224, Issue 4650, 753-755
Copyright © 1984 by American Association for the Advancement of Science

articles

Progressive accumulation of toxic metabolite in a genetic leukodystrophy

H Igisu and K Suzuki

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.


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Functions of sphingolipids and sphingolipid breakdown products in cellular regulation.
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Donor-derived cells in the central nervous system of twitcher mice after bone marrow transplantation.
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Globoid Cell Leukodystrophy: Cranial Computed Tomography and Evoked Potentials.
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