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  • Updated 03.06.2022
  • Released 06.20.1994
  • Expires For CME 03.06.2025

Canavan disease

Introduction

Overview

Canavan disease is a leukodystrophy that causes progressive degeneration, resulting in a spongy deterioration of the brain. The disease is due to mutations in the ASPA gene (OMIM *608034), which encodes aspartoacylase, an enzyme that catalyzes the conversion of N-acetylaspartic acid to aspartate and acetate. In this article, the authors present the history of Canavan disease, current understanding of the pathophysiology, diagnostic work-up, and new therapies that are being developed to treat this rare and devastating condition.

Key points

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

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

• Diagnosis of Canavan disease can be achieved through imaging, biochemistry, and molecular assay.

• Brain magnetic resonance imaging (MRI) findings in patients with Canavan disease show early involvement of the subcortical U-fibers. Magnetic resonance spectroscopy (MRS) shows an elevated N-acetylaspartate peak.

• Carrier screening is recommended for people of Ashkenazi Jewish descent.

• New therapies, including new gene therapies, are currently being investigated for Canavan disease.

Historical note and terminology

Canavan disease, or Canavan-Van Bogaert-Bertrand disease, was first described in 1931 by Myrtelle Canavan (13). The description by Canavan subsequently dominated the American medical literature when spongy degeneration of the brain came to be recognized as a specific entity. A detailed report of three Jewish children with spongy degeneration of the brain was published in 1949 and is widely quoted in the European literature (59). Since then, numerous cases of Canavan disease have been reported, and Canavan disease has been shown to have a higher prevalence in the Ashkenazi Jewish population (06).

The enzyme responsible for Canavan disease, aspartoacylase, was identified by Matalon and colleagues in 1988 (41). The gene was cloned in 1993 (29). As a result of these advancements, mutations can now be identified in patients, family members, and at-risk populations (29; 39). Additionally, the understanding that deficiency of aspartoacylase leads to increased concentration of N-acetylaspartic acid in CSF, serum, and urine has enabled the diagnosis of Canavan disease through biochemical methods.

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