Canavan disease (CD) is an autosomal recessive disorder found mainly in Ashkenazi Jewish families and is caused by deficiency in the activity of the enzyme aspartoacylase (for review, see Reference 30). The pathophysiologic relationship between the loss of this enzymatic activity and the development of CD remains to be elucidated. Diagnosis usually is established by the demonstration of increased levels of the substrate N-acetylaspartic acid in urine because enzymatic studies have been shown to be quite variable. Clinical symptoms associated with CD include macrocephaly, hypotonia, severe developmental delay, optic atrophy, poor head control, and death in childhood.
The gene encoding aspartoacylase (ASPA), located on the short arm of chromosome 17, is relatively small, with 6 exons spanning 30 kb of genomic sequence. Two point mutations, E285A and Y231X, are responsible for more than 97% of mutant alleles in Ashkenazi Jews. Mutations in non-Jewish individuals are more heterogeneous; however, a panethnic mutation, A305E, accounts for approximately 40% to 48% of non-Jewish European alleles.31
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