Canavan Disease: A Neurometabolic Disease Caused By Aspartoacylase Deficiency

Year 2011, Volume: 3 Issue: 1, 1 - 11, 01.01.2011

Ute Lıenhard Jörn Sass

Abstract

Canavan disease is a genetic neurodegenerative disorder caused by mutations in the ASPA gene encoding aspartoacylase, also known as aminoacylase 2. Important clinical features comprise progressive psychomotor delay, macrocephaly, muscular hypotonia as well as spasticity and visual impairment. Cerebral imaging usually reveals leukodystrophy. While it is often expected that patients with Canavan disease will die in childhood, there is increasing evidence for heterogeneity of the clinical phenotype. Aspartoacylase catalyzes the hydrolysis of N-acetylaspartate (NAA) to aspartate and acetate. Its deficiency leads to accumulation of NAA in the brain, blood, cerebrospinal fluid and in the urine of the patients. High levels of NAA in urine are detectable via the assessment of organic acids by gas chromatography - mass spectrometry. Confirmation is available by enzyme activity tests and mutation analyses. Up to now, treatment of patients with Canavan disease is only symptomatic. Although it is a panethnic disorder, information on affected individuals in populations of other than Ashkenazi Jewish origin is rather limited. Ongoing research aims at a better understanding of Canavan disease (and of related inborn errors of metabolism such as aminoacylase 1 deficiency). Unraveling underlying mechanisms may provide a basis for future therapeutic approaches.

Keywords

Canavan disease, aspartoacylase, aminoacylase, leukodystrophy, neurodegeneration, organic acids, N-acetylaspartate, ASPA, ACYI, NAT8L

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