Canavan’s spongiform leukodystrophy
- 189 Downloads
Canavan disease (CD) is a globally distributed early-onset leukodystrophy. It is genetic in nature, and results from an autosomally inherited recessive trait that is characterized by loss of the axon’s myelin sheath while leaving the axons intact, and spongiform degeneration especially in white matter. There is also a buildup of N-acetyl-l-aspartate (NAA) in brain, as well as NAA acidemia and NAA aciduria. The cause of the altered NAA metabolism has been traced to several mutations in the gene for the production of aspartoacylase, located on chromosome 17, which is the primary enzyme involved in the catabolic metabolism of NAA. In this review, an attempt is made to correlate the change in NAA metabolism that results from the genetic defects in CD with the processes involved in the development of the CD syndrome. In addition, present efforts to counter the results of the genetic defects in this disease are also considered.
Index EntriesAspartoacylase astrocytes brain canavan disease leukodystrophy N-acetylaspartate oligodendrocytes
Unable to display preview. Download preview PDF.
- Baslow M. H., Suckow R. F., and Hungund B. L., (2000) Effects of ethanol and of alcohol dehydrogenase inhibitors on the reduction of N-acetylaspartate levels of brain in mice in vivo: A search for substances that may have therapeutic value in the treatment of Canavan disease, an autosomally inherited recessive CNS disease. J. Inher. Metal. Dis. 23(7), 684–692.CrossRefGoogle Scholar
- Canavan M. M. (1931) Schilders encephalitis periaxialis diffusa. Report of a case in a child aged sixteen and one-half months. Arch. Neurol. Psychiat. 25, 299–308.Google Scholar
- Einheber S., Zanazzi G., Ching W., Scherer S., Milner T. A., Peles E., and Salzer J. L. (1997) The axonal membrane protein Caspr, a homologue of Neurexin IV, is a component of the septate-like paranodal junctions that assemble during myelination. J. Cell Biol. 139(6), 1495–1506.PubMedCrossRefGoogle Scholar
- Huang W., Wang H., Kekuda R., Fei Y., Friedrich A., Wang J., et al. (2000) Transport of N-acetylaspartate by Na+-dependent high-affinity dicarboxylate transporter NaDC3 and its relevance to the expression of the transporter in the brain. J. Pharmacol. Exp. Therapeut. 295 (1), 392–403.Google Scholar
- Kinzley H. (1967) The enzymatic synthesis of N-acetyl-l-aspartic acid by a water-insoluble preparation of a cat brain acetone powder. J. Biol. Chem. 242, 4619–4622.Google Scholar
- Leone P., Janson C. G., McFhee S. J., and During M. J. (1999) Global CNS gene transfer for a childhood neurogenetic enzyme deficiency: Canavan disease. Curr. Opin. Mol. Therap. 1(4), 487–492.Google Scholar
- Matalon R. (1997) Canavan disease: diagnosis and molecular analysis. Genet. Testing 1(1), 21–25.Google Scholar
- Shinar Y., Solomon S., Brenner T., McMorris F. A., Yatziv S., and Barash V. (1995) Aspartoacylase activity in rat glial cultures: correlation with 2′,3′-cyclic nucleotide 3′-phosphodiesterase activity. J. Neurochem. 64 (suppl.), S 12 C.Google Scholar
- Sugahara K., Jianying Z., and Kodama H. (1994) Liquid chromatographic-mass spectrometric analysis of N-acetylamino acids in human urine. J. Chromatog. B 657, 15–21.Google Scholar
- Tallan H. H., Moore S., and Stein W. H. (1956) N-Acetyl-l-aspartic acid in brain. J. Biol. Chem. 224, 41–45.Google Scholar