Canavan disease

Canavan disease typically presents with developmental delay, macrocephaly and seizures. It has the highest prevalence in Ashkenazi Jewish populations.

Neonatal/infantile (features are more severe)

• Hypotonia and head lag.
• Developmental delay and regression of skills.
• Feeding difficulties.
• Macrocephaly (from around six months).
• Progressive visual impairment.
• Seizures
• Irritability and sleep disturbance.
• Increasing spasticity (presentation is similar to cerebral palsy).
• Life limiting, with most not surviving childhood.

Juvenile (features are milder)

• Mild speech and/or motor delay.
• No regression and normocephalic.
• Retinitis pigmentosa and seizures (though this is rare).

Canavan disease occurs due to pathogenic variants in both copies of the aspartoacylase (ASPA) gene located on the short arm of chromosome 1. The gene encodes aspartoacylase, an enzyme which metabolises N-acetylaspartic acid. Two founder variants account for 98% of cases in Ashkenazi Jewish populations.

For information about testing, see Presentation: Child with macrocephaly and Presentation: Child with developmental delay or intellectual disability.

Canavan disease is an autosomal recessive condition. The parents of affected individuals are carriers of the condition and therefore have a 25% (one-in-four) chance of having another affected child.

The carrier frequency for Canavan disease in the Ashkenazi Jewish population is over 1-in-40. For this reason, wherever one or both individuals in a couple from this background is a known carrier of the disorder, the couple may be eligible for R246 Carrier testing at population risk for partners of known carriers of nationally agreed autosomal recessive disorders.

Management of children with Canavan disease is complex and should be delivered via a multidisciplinary team, with detailed suggested approaches published by several authors (see our resources list).

Experimental research into developing gene therapy is ongoing.

For clinicians

• GeneReviews: Canavan disease
• Genomics England: NHS Genomic Medicine Service (GMS) Signed Off Panels Resource
• National Institute of Neurological Disorders and Stroke: Canavan disease
• NHS England: National Genomic Test Directory
• OMIM: 271900 Canavan disease
• U.S. National Library of Medicine: ClinicalTrials.gov database

References:

• Bley A, Denecke J, Kohlschütter A and others. ‘The natural history of Canavan disease: 23 new cases and comparison with patients from literature’. Orphanet Journal of Rare Diseases 2021: volume 16, issue 1, page 227. DOI: 10.1186/s13023-020-01659-3

For patients

• Canavan Foundation: Resources and support