Leukodystrophies Krabbe’s Disease

Diagnosis of Globoid Cell Leukodystrophy (Krabbe s Disease)". Blochem. Blophys. Res. Commun., (1971), 1363-1366. 

Globoid cell leukodystrophy (Krabbe s disease) Galactosylceramidase Galactosylsphingosine Galactosylceramide... 

Suzuki K. Biochemical pathogenesis of genetic leukodystrophies comparison of metachromatic leukodystrophy and globoid cell leukodystrophy (Krabbe s disease). Neuropediatrics 1984 15 32-36. 

Further reading Suzuki, K. and Suzuki, Y. (1978). Galacto-sylceramide lipidosis. Globoid cell leukodystrophy (Krabbe s disease). In Stanbury, J.B., Wyngaarden, J.B. and Fredrickson, D.S. (eds.) The Metabolic Basis of Inherited Disease, 4th Edn., p. 747. (New York McGraw-Hill)... 

In globoid cell leukodystrophy (Krabbe s disease) in the central nervous system, the level of sulfatide is decreased and that of cere-broside increased as compared to normal conditions. The disorder is caused by a deficiency of a cerebroside sulfotransferase (Bachhawat et al., 1967). Familial globoid cell leukodystrophy is not restricted to humans, but occurs also in dogs (Fankhauser, 1963 Fletcher, 1966 Hirth and Nielsen, 1967). 

Other leukodystrophies are associated with the lysosomal and peroxisomal disorders in which specific lipids or other substances accumulate due to a deficiency in a catabolic enzyme - for example Krabbe s disease, meta-chromatic leukodystrophy (MLD) and adrenoleuko-dystrophy (ALD) [1,2]. (These are discussed in detail in Ch. 40.) Similarly, disorders of amino acid metabolism can lead to hypomyelination - for example phenylketonuria and Canavan s disease (spongy degeneration) [1, 2, 25] (Ch. 40). The composition of myelin in the genetically... 

Figure 9.20 Degradation of sphingolipids. Lipid storage diseases are indicated by brackets as follows TS, Tay-Sachs ML, metachromatic leukodystrophy GG, generalized gangliosidosis G, Gaucher s disease NP, Niemann-Pick disease K, Krabbe s disease F, Fabry s disease. The sulfate residue on galactocerebroside is located on position 3 of the galactose residue. Note the sequential nature of the process if one step cannot take place, all subsequent steps cannot take place, either.

In Krabbe s disease (globoid leukodystrophy) there is accumulation of galactocerebroside in the white matter of the diild s nervous system, as lysosomes lack the enzyme galactoceiebrosid. There is poor myelinization, optic atrophy, mental retardation and, typically, death within 1-2 years of the condition s onset in in ncy. 

Krabbe s disease (Globoid leukodystrophy) Mental retardation, almost total absence of myelin, globoid bodies in white matter of brain Galactocerebroside Galactocerebroside -galactosidase... 

Krabbe S disease, or Krabbe s leukodystn hy, or Galactosylceramide lipidosis, or Globoid cell leukodystrophy (a sphingolipidosis) (see Fig. 3). 

Krabbe s Disease, or Globoid Lipoidosis. The brain of these patients usually appears normal, except for a reduction in size. On section, leukodystrophy of the centrum ovale, the brain stem, and the cerebellum is detectable. Histologically, demyelinization, astrocy-... 

Cerebrosides and sphingomyelin are believed to accumulate in the globoid bodies. In fact, the injection of cerebrosides into rats has led to the appearance in the white matter of cells that resemble globoid cells. The biochemical defect in Krabbe s disease is still unknown, but two clues are available. There are no defects in sphingomyelin breakdown, there is a shift in the ratio of cerebrosides to sulfatides (from 3 to 1 in the normal individuals to 12 to 1 in those with leukodystrophy. These observations have led to the suggestion [127-130] that the lipidosis results from a deficiency of a sulfate-transferring enzyme (see Fig. 3-43). 

A group of inherited diseases in which there are deficiencies of specific lysosomal hydrolases. The diseases are characterized by the deposition of complex lipids. They include Gaucher s disease, Fabry s disease, Krabbe s disease, Tay-Sachs disease, generalized gangliosidosis, Niemann-Pick disease and metachromatic leukodystrophy. 

Lysosomal storage abnormalities, such as glycogenosis (Pompe s disease). Tay-Sachs, Krabbe s. Gaucher s, and Fabry s diseases, as well as melachromatic leukodystrophy, aspariylgiycosaminuria, and Niemann-Pick disease. Also included in this category are mucopolysaccharidoses. Hunter s, Scheie s, and Hurler s syndromes. 

R. Koike, S. Tsuji, Y. Fukumaki, K. Hayashi, and T. Kobayashi. 1997. Adult onset globoid cell leukodystrophy (Krabbe disease) Analysis of galactosylceramidase cDNA from four Japanese patients. Hum Genet 100 450-456. 

Lyon, G., B. Hagberg, P. Evrard, C. Allaire, L. Pavone, and V. M. 1991. Symptomatology of late onset Krabbe s leukodystrophy The European experience. Dev Neurosci 13 240-244. Maestri, N. E., and T. H. Beaty. 1992. Predictions of a 2-locus model for disease heterogeneity Application to adrenoleukodystrophy. Am J Hum Genet 44 576-582. 

Suzuki, K., 1977, Globoid cell leukodystrophy (Krabbe disease) and GMl-gangliosidosis, in Practical Enzymology of the Sphingolipidoses (R. H. Glew and S. P. Peters, eds.), Liss, New York, pp. 101-136. 

Kolodny, E. H., S. Raghavan, and W. Krivit. 1991. Late-onset Krabbe disease (globoid cell leukodystrophy) Clinical and biochemical features of 15 cases. Dev Neurosci 13 232-239. Korenke, G. C., H. J. Christen, B. Kruse, D. H. Hunneman, and F. Hanefeld. 1997. Progression of X-linked adrenoleukodystrophy under interferon-I therapy. J Inherit Metab Dis V20 59-66. Krabbe, K. 1916. A new familial, infamtUe form of diffuse brain sclerosis. Brain 39 74-114. 

Lees, M. B., and H. W. Moser The chemical pathology of Krabbe disease and metachromatic leukodystrophy. In Cerebral sphingolipidoses, p. 179. Eds S.M. Aronson and B. W. Volk. New York-London Academic Press 1962. 

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