Canavan disease

Also known as: Canavan-Van Bogaert-Bertrand disease; Van Bogaert-Bertrand syndrome; Von Bogaert-Bertrand disease

Background

Canavan disease is a rare genetic condition that affects the nervous system. It is a leukodystrophy coming from the Greek words, ‘leuko’ meaning white and ‘dystrophy’ meaning imperfect growth or development. There are different types of Canavan disease which include congenital (present at birth), infantile, and late-onset forms. In Canavan disease, there is widespread degeneration of the white matter in the brain leading to loss of sensory, motor and intellectual function. The white matter of the brain has nerves with a fatty covering (myelin sheath) which acts as an insulator around the fibres and helps them work properly.

Credits

Last updated February 2015 by Dr Alasdair Parker, Addenbrooke’s Hospital and University of Cambridge School of Clinical Medicine, Cambridge, UK.

What are the symptoms?

Babies appear normal in the first few months of life. However, in early infancy they begin to lose previously acquired skills, including seeing and hearing. In some children, the head becomes progressively enlarged (megalencephaly) as the brain swells and the bones of the skull fail to fuse. Babies may lose control of their muscles, including those supporting the head, so the neck becomes floppy and weak (known as hypotonia).

Sitting, standing and walking are rarely achieved by affected children. Although speech is delayed, infants are able to interact socially. Learning difficulties become more severe over time. As children become older, floppiness of the muscles gives way to spasticity (stiffness of the limbs). After the first or second year of life, feeding difficulties become apparent.

What are the causes?

Canavan disease is caused by changes (or mutations) in the ASPA gene on chromosome 17. This gene provides instructions for making an enzyme called aspartoacylase that processes the chemical N-acetylaspartate (NAA).

How is it diagnosed?

The condition is more common in people of Ashkenazi Jewish ancestry. Canavan disease may be suspected on the basis of a magnetic resonance imaging (MRI) scan showing swelling and degeneration of the white matter of the brain. Special settings may allow the disease to be identified with reasonable confidence (if suspected) by magnetic proton spectroscopy, which allows the excess NAA to be identified. The NAA level can also be assessed by a urine test.

How is it treated?

Affected children will require supportive treatments to improve quality of life and aid comfort. These will include:

  • physiotherapy and occupational therapy to aid mobility and help with loss of skills
  • speech therapy to help communication and swallowing
  • a gastrostomy (feeding tube through the skin into the stomach) may be needed to help infants with feeding problems get the nutrition they need
  • a community paediatrician to assess and coordinate local care
  • a social worker to help integrate other local services e.g. education.

Three new treatments are currently under investigation:

  1. gene therapy to replace the mutated ASPA gene
  2. metabolic therapy to provide a crucial missing metabolite (acetate)
  3. enzyme therapy where aspartoacylase is engineered to be able to enter the brain. 

It is important to point out that the results from these trials are not conclusive and many more years of development will be needed.

There are many posts on the internet reporting the life expectancy of children with Canavan. However, many of these are based on information that was supplied before the onset of good multidisciplinary care, so it is recommended that this should be discussed with an expert in Canavan such as a paediatric neurologist or metabolic specialist, and every child should be considered separately.

Inheritance patterns and prenatal diagnosis

Inheritance patterns
Canavan disease is inherited as an autosomal recessive trait. Affected families should be referred to a genetics centre for information and suppor.

Prenatal diagnosis
This is possible if the genetic mutation in the family is known.

Is there support?

Information and support in the UK for Canavan disease is provided by Metabolic Support UK (see entry Inherited Metabolic diseases).

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