DOI: 10.1126/science.6719111. Progressive Accumulation of Toxic Metabolite in a Genetic Leukodystrophy

Progressive Accumulation of Toxic Metabolite in a Genetic Leukodystrophy

10.1126/science.6719111

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

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). Galactosylsphingosine 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.

Bibliography

Igisu, H., & Suzuki, K. (1984). Progressive Accumulation of Toxic Metabolite in a Genetic Leukodystrophy. Science, 224(4650), 753â755.

Authors 2

Hideki Igisu (first)
Kunihiko Suzuki (additional)

References 17 Referenced 205

CARRUTHERS, A, UDP-GALACTOSE - CERAMIDE GALACTOSYL TRANSFERASE OF ISOLATED OLIGODENDROGLIA, JOURNAL OF NEUROCHEMISTRY 41: 22 (1983). (10.1111/j.1471-4159.1983.tb11810.x) / JOURNAL OF NEUROCHEMISTRY (1983)
DESHMUKH, D.S., BIOSYNTHESIS AND CONCENTRATION OF GALACTOSYL DIGLYCERIDE IN GLIAL AND NEURONAL ENRICHED FRACTIONS OF ACTIVELY MYELINATING RAT-BRAIN, JOURNAL OF NEUROCHEMISTRY 22: 479 (1974). (10.1111/j.1471-4159.1974.tb06882.x) / JOURNAL OF NEUROCHEMISTRY (1974)
HERS, H.G., GASTROENTEROLOGY 48: 625 (1966). / GASTROENTEROLOGY (1966)
IGISU, H, LIPIDS OF DEVELOPING BRAIN OF TWITCHER MOUSE - AN AUTHENTIC MURINE MODEL OF HUMAN KRABBE DISEASE, BRAIN 106: 405 (1983). (10.1093/brain/106.2.405) / BRAIN (1983)
IGISU, H, TRANSACTIONS OF THE AMERICAN SOCIETY FOR NEUROCHEMISTRY 15: 104 (1984). / TRANSACTIONS OF THE AMERICAN SOCIETY FOR NEUROCHEMISTRY (1984)
IGISU H unpublished data.
KOBAYASHI, T, THE TWITCHER MOUSE - DETERMINATION OF GENETIC STATUS BY GALACTOSYLCERAMIDASE ASSAYS ON CLIPPED TAIL, BIOCHEMICAL MEDICINE 27: 8 (1982). (10.1016/0006-2944(82)90003-5) / BIOCHEMICAL MEDICINE (1982)
KOBAYASHI, T, THE TWITCHER MOUSE - AN ENZYMATICALLY AUTHENTIC MODEL OF HUMAN GLOBOID-CELL LEUKODYSTROPHY (KRABBE DISEASE), BRAIN RESEARCH 202: 479 (1980). (10.1016/0006-8993(80)90159-6) / BRAIN RESEARCH (1980)
MIYATAKE, T, GLOBOID CELL LEUKODYSTROPHY - ADDITIONAL DEFICIENCY OF PSYCHOSINE GALACTOSIDASE, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 48: 538 (1972). (10.1016/0006-291X(72)90381-6) / BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (1972)
MIYATAKE, T, GALACTOSYLSPHINGOSINE GALACTOSYL HYDROLASE - PARTIAL PURIFICATION AND PROPERTIES OF ENZYME IN RAT-BRAIN, JOURNAL OF BIOLOGICAL CHEMISTRY 247: 5398 (1972). (10.1016/S0021-9258(20)81118-1) / JOURNAL OF BIOLOGICAL CHEMISTRY (1972)
MIYATAKE, T, GALACTOSYLSPHINGOSINE GALACTOSYL HYDROLASE IN RAT-BRAIN - PROBABLE IDENTITY WITH GALACTOSYLCERAMIDE GALACTOSYL HYDROLASE, JOURNAL OF NEUROCHEMISTRY 22: 231 (1974). (10.1111/j.1471-4159.1974.tb11584.x) / JOURNAL OF NEUROCHEMISTRY (1974)
NILSSON, O, ACCUMULATION OF GLUCOSYLCERAMIDE AND GLUCOSYLSPHINGOSINE (PSYCHOSINE) IN CEREBRUM AND CEREBELLUM IN INFANTILE AND JUVENILE GAUCHER DISEASE, JOURNAL OF NEUROCHEMISTRY 39: 709 (1982). (10.1111/j.1471-4159.1982.tb07950.x) / JOURNAL OF NEUROCHEMISTRY (1982)
RAGHAVAN, S.S., ISOLATION AND CHARACTERIZATION OF GLUCOSYLSPHINGOSINE FROM GAUCHERS SPLEEN, JOURNAL OF LIPID RESEARCH 15: 484 (1974). (10.1016/S0022-2275(20)36768-7) / JOURNAL OF LIPID RESEARCH (1974)
SUZUKI, K, METABOLIC BASIS INHE: 857 (1983). / METABOLIC BASIS INHE (1983)
SUZUKI, K, GLOBOID CELL LEUCODYSTROPHY (KRABBES DISEASE) - DEFICIENCY OF GALACTOCEREBROSIDE BETA-GALACTOSIDASE, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 66: 302 (1970). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1970)
SUZUKI, Y, STUDIES IN GLOBOID LEUKODYSTROPHY - ENZYMATIC AND LIPID FINDINGS IN CANINE FORM, EXPERIMENTAL NEUROLOGY 29: 65 (1970). (10.1016/0014-4886(70)90037-3) / EXPERIMENTAL NEUROLOGY (1970)
SVENNERHOLM, L, KRABBE DISEASE - GALACTOSYLSPHINGOSINE (PSYCHOSINE) LIPIDOSIS, JOURNAL OF LIPID RESEARCH 21: 53 (1980). (10.1016/S0022-2275(20)39839-4) / JOURNAL OF LIPID RESEARCH (1980)

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 3:41 p.m.)
Deposited	1 year, 7 months ago (Jan. 14, 2024, 5:47 p.m.)
Indexed	3 days, 20 hours ago (Aug. 29, 2025, 6:12 a.m.)
Issued	41 years, 3 months ago (May 18, 1984)
Published	41 years, 3 months ago (May 18, 1984)
Published Print	41 years, 3 months ago (May 18, 1984)

Funders 0

None

BibTeX

@article{Igisu_1984, title={Progressive Accumulation of Toxic Metabolite in a Genetic Leukodystrophy}, volume={224}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.6719111}, DOI={10.1126/science.6719111}, number={4650}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Igisu, Hideki and Suzuki, Kunihiko}, year={1984}, month=may, pages={753–755} }

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