Genetic diseases leukodystrophies

A genetic disease, the 18q-syndrome is a rare leukodystrophy presenting a genomic deletion that includes the MBP gene. Proton magnetic resonance data indicate demyelination or increased myelin turnover rather than dysmyelination (Hausleretal., 2005). 

In the human genetic disease X-linked adreno-leukodystrophy (ADL), peroxisomal oxidation of very long chain fatty acids is defective. The ADL gene encodes the peroxisomal membrane protein that trans-... 

The human leukodystrophies are inherited disorders of central nervous system white matter. These disorders are characterized by a diffuse deficiency of myelin caused by a variety of genetic lesions and often manifest before 10 years of age (Table 38-1). Some are caused by mutations in the PLP gene and resemble the PLP animal mutants described in Chapter 4 [ 1,23]. As with the animal models, depending on the nature of the mutation, they vary from a severe form in connatal Pelizaeus-Merzbacher disease (PMD) through an intermediate phenotype in classical PMD to a mild phenotype in spastic paraplegia. It is noteworthy that some mutations of the PLP gene also cause a peripheral neuropathy [24], very probably related to the expression of low levels of PLP in peripheral nerve (see Ch. 4). 

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... 

Rafi MA, Coppola S, Liu SL, Rao HZ, Wenger DA (2003) Disease-causing mutations in cis with the common arylsulfatase A pseudodeficiency allele compound the difficulties in accurately identifying patients and carriers of metachromatic leukodystrophy. Mol Genet Metab 79 83-90... 

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

The Genetics of Myelination in Metabolic Brain Disease The Leukodystrophies... 

Baslow, M. 2000. Canavan s spongiform leukodystrophy A clinical anatomy of a genetic metabolic CNS disease — An analytical review. J. Mol. Neurosci 15 61-69. 

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., and K. Suzuki. 1985. Genetic galactosylceramidase deficiency (globoid cell leukodystrophy, Krabbe disease) in different mammalian species. Neurochem Pathol 3 53-68. 

Wenger, D. A., M. A. Rafi, and P. Luzi. 1997. Molecular genetics of Krabbe disease (globoid ceU leukodystrophy) Diagnostic and clinical implications. Hum Mutat 10 268-279. 

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