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Aspartoacylase deficiency (Canavan disease)

Raphael Schiffmann, MD, MHSc
Section Editors
Marc C Patterson, MD, FRACP
Francisco González-Scarano, MD
Deputy Editor
John F Dashe, MD, PhD


Aspartoacylase deficiency (Canavan disease; MIM #271900) is an autosomal recessive spongiform leukodystrophy that is prevalent in, but not restricted to, Ashkenazi Jewish individuals. The disease typically begins in infancy and is marked by relentless progression.

Canavan disease was first described in the early 20th century as spongy degeneration of central nervous system myelin in infancy. The discovery of N-acetylaspartic aciduria due to aspartoacylase deficiency in a leukodystrophy was made in 1987 [1]. The realization that this leukodystrophy was actually Canavan disease with abnormal N-acetylaspartic acid (NAA) metabolism was not made until 1988 [2]. Elevated urinary NAA excretion and aspartoacylase deficiency had been reported two years previously, but without a direct association to spongy degeneration of myelin in infancy [1]. The aspartoacylase gene was cloned in 1993, and numerous mutations have been identified since then [3-6].

Although the Canavan disease eponym is widely used, aspartoacylase deficiency is preferable. Of interest, Canavan's own report was linked to Schilder disease or Krabbe disease (galactocerebrosidase deficiency) and not spongy degeneration.


Aspartoacylase deficiency is caused by mutations in the ASPA gene that encodes the enzyme aspartoacylase. The resulting deficiency of aspartoacylase leads to accumulation of N-acetylaspartic acid (NAA) in the brain and to oligodendrocyte dysfunction, spongiform changes, and absence of myelin. However, the precise mechanisms causing spongiform degeneration are uncertain.

Genetics — Aspartoacylase deficiency is transmitted in an autosomal recessive fashion. The gene encoding aspartoacylase (ASPA) is located on chromosome 17pter-p13 [4]. Several mutations have been defined in ASPA, but just four of them account for >99 percent of aspartoacylase deficiency cases in Ashkenazi Jews [3,5,7-10].

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Literature review current through: Nov 2017. | This topic last updated: Jun 05, 2017.
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