Krabbe’s disease

Krabbe s disease P-Gaiactosidase Cer-i-Gai Gaiactosyiceramide Mental retardation myelin almost absent. 

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

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... 

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

Studies on Krabbe s disease and GM 1-gangliosidosis have contributed a great deal to our understanding of the catabolism of glycosphin-... 

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.

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

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 Demyelination, mental retardation Galactocerebroside /3-Galactosidase... 

The D-galactosylceramide jS-D-galactosidase from the liver of a case of Krabbe s disease has been purified. The physical properties of this enzyme were very similar to those of a control from normal liver tissue but the catalytic properties and stability of the enzyme protein were severely affected in the mutant. The findings indicated that the mutation in Krabbe s disease leads to the synthesis of normal quantities of a catalytically and structurally altered protein. 

In p-galactosidase II deficiency, GL-2a (Gaipi,4Glcpi,lCer) is the storage product. Unlike Krabbe s disease, it is the grey matter, rather than the white matter, which is affected. The liver, spleen, bone marrow and lymph nodes are all involved. It is by no means certain that this disease is a simple P galactosidase deficiency or that all cases are alike. 

Hagberg, B., H. Kollberg, P. Sourander, and H. O. Akesson. 1970. Infantile globoid ceU leucodys-trophy (Krabbe s disease) A clinical and genetic study of 32 Swedish cases 1953-1967. 

Sabatelli, M., L. Quaranta, F. Madia, G. Lippi, A. Conte, M. Lo Monaco, G. Di Trapani, M. A. Rafi, D. A. Wenger, A. M. Vaccaro, and P. Tonali. 2002. Peripheral neuropathy with hypomyelinating features in adult-onset Krabbe s disease. Neuromuscul Disord 12 386-391. 

Zarifi, M. K., A. A. Tzdka, L. G. Astrakas, T. Y. Poussaint, D. C. Anthony, and B. T. Darras. 2001. Magnetic resonance spectroscopy and magnetic resonance imaging findings in Krabbe s disease. J Child Neurol 16 522-526. 

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

Most of the early tests were based on the hydrolysis of the natural sphingolipid which had been labelled in the hydrophilic portion. Thus, the substrate and products could be easily separated by two-phase solvent partition or by precipitation of the product. In many cases artificial chromogenic or fluorogenic glycosides could be used instead of radiolabelled substrates. However, in these cases it is very important to demonstrate that the conditions and specificities of the enzynie reactions are such that the results can be extrapolated to the natural substrate (e.g. Peters et al., 1975). Thus, in the case of Niemann-Pick or Krabbe s diseases the unsubstituted... 

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