Canavan disease

Reuben Matalon MD PhD (Dr. Matalon of University of Texas Medical Branch has no relevant financial relationships to disclose.)
Lisvania M Delgado BS (

Ms. Delgado of Trinity School of Medicine has no relevant financial relationships to disclose.

Brianna M Young MS2 (

Mrs. Young of Trinity School of Medicine has no relevant financial relationships to disclose.

Dena Rae Matalon MD (

Dr. Matalon of Stanford University has no relevant financial relationships to disclose.

Raphael Schiffmann MD, editor. (Dr. Schiffmann, Director of the Institute of Metabolic Disease at Baylor Research Institute, received research grants from Amicus Therapeutics, Protalix Biotherapeutics, and Sanofi Genzyme.)
Originally released June 20, 1994; last updated May 25, 2019; expires May 25, 2022

This article includes discussion of Canavan disease, spongy degeneration of the brain, Van Bogaert-Bertrand disease, autosomal recessive, N-acetyl aspartate (NAA) in brain white matter, and developmental psychology of Canavan disease and the community. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Canavan disease is degenerative neurologic condition characterized by aspartoacylase deficiency, resulting in a spongy deterioration of the brain. Leukodystrophies are hereditary metabolic diseases in which the underlying biochemical abnormalities lead to defect of myelination. Canavan disease is due to mutations in the ASPA gene (OMIM *608034) encoding the aspartoacylase enzyme that catalyzes the conversion of acetylaspartic acid (NAA) to aspartate and acetate. In this article, the authors present new information on the expanding spectrum of Canavan disease phenotype. Atypical Canavan disease patients have minimal delays and MRI findings typical of mitochondrial disorders. In the area of treatment, trials with gene therapy using an AAV2 vector and supplementation with acetate are some of the interventions being used experimentally. Enzyme replacement therapy with recombinant aspartoacylase showed an increase in the enzyme activity in the brain of the treated Canavan knockout mouse. Novel rAAV serotypes AAV 8, 9, and 10 cross the blood-brain barrier. These serotypes were used to correct the phenotype and brain problems in the knockout Canavan disease mouse.

Key points


• Aspartoacylase deficiency leads to spongy degeneration of the white matter.


• Aspartoacylase deficiency leads to increased N-acetylaspartic acid in blood, tissues, and urine.


• Diagnosis of Canavan disease can be achieved by examining urine N-acetylaspartic acid (NAA).


• Aspartoacylase is essential for proper myelination.


• Prevention by carrier testing is recommended for Ashkenazi Jews.


• Improving the understanding of the nature of structural defects provides a basis for the development of treatment therapies for Canavan disease.

Historical note and terminology

Spongy degeneration of white matter of the brain, Canavan disease, was described in 1931 by Canavan (Canavan 1931). The description of spongy degeneration of the brain by Canavan was thought to represent Schilder disease in a child. An earlier report in 1928 described similar brain pathology and was also thought to be a case of Schilder disease (Globus and Strauss 1928). The description by Canavan has dominated the American medical literature when spongy degeneration of the brain came to be recognized as a specific entity. A detailed report of 3 Jewish children with spongy degeneration of the brain was published in 1949 and is widely quoted in the European literature (van Bogaert and Bertrand 1949). Since then, numerous cases have been reported, with prevalence among Jewish individuals (Banker and Victor 1979). The enzyme defect of Canavan disease was identified by Matalon and colleagues in 1988 (Matalon et al 1988). Deficiency of aspartoacylase leads to increased urinary excretion of N-acetylaspartic acid, making the diagnosis of Canavan disease easy to ascertain. The gene for Canavan disease was cloned in 1993, and mutations can now be determined in patients, family members, and at-risk populations (Kaul et al 1993; Matalon et al 1993).

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