CANAVAN DISEASE - BIOCHEMICAL AND MOLECULAR STUDIES

Deficiency of the enzyme aspartoacylase and the accumulation of N-acet ylaspartic acid lead to a severe leukodystrophy and spongy degeneratio n of the brain, Canavan disease (McKusick 271900). Since our discovery in 1988 of the defect in Canavan disease, 144 patients with Canavan d isease have been diagnosed in our laboratory. Most of these children a re 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 cultu red chorionic villus samples or amniocytes. The determination of N-ace tylaspartic acid in the amniotic fluid is another parameter for diagno sis; however, the levels may not always be elevated. Bovine and human aspartoacylase have been purified in our laboratory. Bovine and human cDNA and genomic clones have been isolated and six exons have been loc alized. This information is being used for the study of Canavan diseas e at the molecular level.