PRENATAL-DIAGNOSIS FOR CANAVAN DISEASE - THE USE OF DNA MARKERS

Canavan disease (CD; McKusick 271900) is a severe autosomal recessive leukodystrophy caused by the deficiency of aspartoacylase and the accumulation in brain of N-acetylaspartate (NAA) (Matalon et al 1988). The clinical course of CD is that of a rapid deterioration and early death (Van Bogaert and Bertrand 1949). Canavan disease is panethnic, with prevalence among individuals of Ashkenazi Jewish extraction. Since the discovery of the enzyme defect, urine NAA levels have been used for the diagnosis of CD, a disease seen with increased frequency. Our preliminary studies on unrelated healthy Jewish individuals suggest that the carrier frequency among Ashkenazi Jews is 1/35 (Matalon et al 1994 and unpublished data). This high ratio of carriers is close to that of Tay - Sachs disease. There is no treatment for CD and the only prevention is through genetic counselling and prenatal diagnosis. The use of amniocytes and chorionic villus samples for aspartoacylase assay proved unreliable because of the very low enzyme activity in these cells (Matalon et al 1992; Bennett et al 1993). Assay for NAA in amniotic fluid seems to hold more promise and is the only method currently available for prenatal diagnosis (Bennett et al 1993; Kelley 1993). Recently the gene for aspartoacylase has been cloned and mutations causing aspartoacylase deficiency have been identified (Kaul et al 1994). Families with known genotype for CD can be studied for prenatal diagnosis. The purpose of this paper is to present such a study on an informative family with CD.