IMR Press / FBL / Volume 5 / Issue 3 / DOI: 10.2741/matalon

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Spongy degeneration of the brain, Canavan disease: biochemical and molecular findings
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1 Department of Pediatrics, University of Texas Medical Branch at Galveston, Galveston, Texas 77555-0359, USA
Academic Editor:Owen Rennert
Front. Biosci. (Landmark Ed) 2000, 5(3), 307–311; https://doi.org/10.2741/matalon
Published: 1 March 2000
(This article belongs to the Special Issue Genetic diseases)
Abstract

Canavan disease is a severe progressive leukodystrophy characterized by swelling and spongy degeneration of the white matter of the brain. It is an autosomal recessive disease found more frequently among Ashkenazi Jews. The clinical features are those of severe mental retardation with inability to gain developmental milestones. Hypotonia, head lag and macrocephaly are characteristic of Canavan disease and become apparent after 5-6 months of age. Massive excretion in the urine of N-acetylaspartic acid is the biochemical marker for Canavan disease, which is caused by deficiency of the enzyme aspartoacylase. This discovery allowed for accurate diagnosis of Canavan disease, while prior to that, a brain biopsy was needed. The gene for aspartoacylase has been cloned and two mutations predominate among Ashkenazi Jewish individuals with Canavan disease and account for more than 98% of the Ashkenazi Jewish patients. The mutations among other ethnic groups are more diverse. The carrier frequency for the two common mutations among Ashkenazi Jews was found to be surprisingly high, 1:37. Screening for carriers is now common practice for this population. A knock-out mouse for Canavan disease is being genetically engineered in our laboratory. The mouse model will allow for development of strategies for gene therapy.

Keywords
N-acetylaspartic acid
aspartoacylase
Canavan disease
Macrocephaly
Spongy Degeneration Of The Brain
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