Krabbes disease

As 1 of the 12 known leukodystrophies, Krabbe disease produces impaired myeiin sheath deveiop-ment with progressive neurodegeneration of both the CNS and the peripherai nervous system. 

Chiidren with Krabbe disease exhibit irritabiiity, fever, seizures, iimb stiffness, deiayed mentai or motor deveiopment, vomiting, feeding difficuities, hypertonia, spasticity, deafness, and biindness. 

The incidence of Krabbe disease is 1 in 100,000 births in the United States. 

Krabbe disease is caused by inherited deficiency of the lysosomal hydrolase galactocerebrosidase, the enzyme responsible for degradation of gaiactosyiceramide, a component of the myelin sheath, and other galactosphingosines (eg, psychosine). 

This enzyme is increased in Gaucher disease and may also be increased, but to a lesser extent, in other sphingolipidoses such as Niemann-Pick disease type A/ and NPC, Krabbe disease, and GM1-gangliosidosis. The assay is based on the method described by Hollak et al. [22] and Guo et al. [17]. 

This enzyme is deficient in Krabbe disease (Table 4.4.1, Fig. 4.4.1). The assay is based on the method described Wiederschain et al. [64] as modified by van Diggelen (unpublished data). 

Wenger DA, Rafi MA, Luzi P, Datto J, Constantino-Cerrarini E (2000) Krabbe disease genetic aspects and progress toward therapy. Mol Genet Metab 70 1-9... 

Gaucher disease, and Krabbe disease. LSDs are classified as mucopolysaccharidoses (MPS), lipidoses, or mucolipidoses depending on the nature of the stored material. Over 40 LSDs are known and they have a collective incidence of approximately 1 in 7000-8000 live births (Meikle et al., 1999 Poorthuis et al., 1999 Winchester et al., 2000). Most of the genes for these lysosomal proteins have been cloned, permitting mutation analysis in individual cases. 

Figure 16-5. The pathway of sphingolipid catabolism. Diseases that result from specific enzyme deficiencies are as follows (1) GM, gangliosidosis (2) GM2 gangliosidosis (Tay-Sachs disease) (3) sialidosis (4) Fabry disease (5) Gaucher disease (6) Niemann-Pick disease (7) Krabbe disease (8) metachromatic leukodystrophy (9) Farber disease. Cer, Ceramide Glc, glucose Gal, galactose GalNAc, A -acetylgalactosamine NANA, N-acetyfiieuraminic acid.

Krabbe disease (Globoid-cell leukodystrophy) Galactosylceramidase Galactosylceramide psycosine... 

Other lysosomal storage disorders include G j gangliosidoses, G gangliosidoses, Gaucher disease, Niemann-Pick disease, Fabry disease, fucosidosis, Schindler disease, metachromatic leukodystrophy, Krabbe disease, multiple sulfatase deficiency, Farber disease, and Wolman disease. Table 28-1 illustrates the enzyme deficiencies found in some of these disorders. 

An autosomal recessive affliction resulting from deficient galactocerebrosidase (GALC, EC 3.2.1.46) activity in the lysosome, Krabbe disease, characterized by... 

Brockmann, K., P. Dechent, B. WUken, O. Rusch, J. Frahm, and F. Hanefeld. 2003. Proton MRS profile of cerebral metabolic abnormalities in Krabbe disease. Neurology 60 819-825. 

Molecular heterogeneity of Krabbe disease. J Inherit Metab Dis 22 155-162. 

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. 

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. 

Loes, D. J., A. E. Stillman, S. Hite, E. Shapiro, L. Lockman, R. E. Latchaw, H. Moser, and W. Krivit. 1994. Childhood cerebral form of adrenoleukodystrophy short-term effect of bone marrow transplantation on brain MR observations. AJNR Am J Neuroradiol 15 1767-1771. Luzi, R, M. A. Rafi, and D. A. Wenger. 1995. Characterization of the large deletion in the GALC gene found in patients with Krabbe disease. Hum Mol Genet 4 2335-2338. 

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