Canavan Disease: Biochemical and Molecular Studies

Deficiency of the enzyme aspartoacylase and the accumulation ofN-acetylaspartic acid lead to a severe leukodystrophy and spongy degeneration of the brain, Canavan disease (McKusick 271900). Since our discovery in 1988 of the defect in Canavan disease, 144 patients with Canavan disease have been diagnosed in our laboratory. Most of these children are of Ashkenazi Jewish extraction. The level of enzyme activity can be used for carrier testing. Prenatal diagnosis has been difficult using the enzyme assay owing to the low activity of aspartoacylase in cultured chorionic villus samples or amniocytes. The determination ofN-acetylaspartic acid in the amniotic fluid is another parameter for diagnosis; however, the levels may not always be elevated.