A Breakthrough in Understanding the Nature of Canavan Disease, a Human Spongiform Leukodystrophy due to Inborn Errors in the Gene Encoding for Aspartoacylase

Canavan disease (CD) is a rare early-onset progressive spongiform leukodystrophy in brain of both humans and animals and is due to mutations in the gene encoding for aspartoacylase (ASPA), the enzyme that hydrolyzes N-acetyl-L-aspartate (NAA) [1]. In humans, the effects of CD are generally much more profound than in rodents exhibiting this same genetic lesion. The gene for ASPA is an autosomal recessive and human or animal carriers of mutations do not appear to be affected. ASPA is expressed in oligodendrocytes and based on their large fractional cellular volume, these cells are the major source of ASPA in brain. However, ASPA has also been identified in microglia and in several other cellular brain compartments [2]. NAA is part of a very unusual tri-cellular metabolic cycle in brain as illustrated in Figure 1.