Canavan disease is an inherited disorder that causes progressive damage to nerve cells in the brain. This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies are characterized by degeneration of myelin, which is the fatty covering that insulates nerve fibers.
The signs and symptoms of this disease usually begin in early infancy; however, the course of the condition can be quite variable. Infants with Canavan disease typically appear normal for the first few months of life. By age 3 to 5 months, affected infants begin having problems with development, including a delay in motor skills such as turning over, controlling head movement, and sitting without support. These infants typically also have weak muscle tone (hypotonia), unusually large head size (macrocephaly), abnormal posture, and intellectual disability. Feeding and swallowing difficulties, seizures, and sleep disturbances may also develop.
The life expectancy for people with Canavan disease varies. Most affected individuals live only into childhood, although some survive into adolescence or beyond.
Mutations in the ASPA gene cause Canavan disease.
The ASPA gene provides instructions for making an enzyme called aspartoacylase. This enzyme normally breaks down a compound called N-acetyl-L-aspartic acid (NAA), which is predominantly found in nerve cells in the brain. Although the precise function of NAA is unclear, it probably plays a role in the production of myelin.
Mutations in the ASPA gene prevent the normal breakdown of NAA. Recent studies suggest that if NAA is not broken down properly, the resulting chemical imbalance may interfere with the formation of myelin as the nervous system develops. A buildup of NAA also leads to the progressive destruction of existing myelin around nerve cells. Nerve fibers without this protective covering malfunction and die, damaging the brain and causing the serious signs and symptoms of Canavan disease.
Genetic counseling is recommended for prospective parents with a family history of Canavan disease, and should be considered if both parents are of Ashkenazi Jewish descent. For this group, DNA testing can almost always tell if one or both parents is a carrier.
The prognosis for Canavan disease is poor. Death usually occurs before age 4, although some children may survive into their teens and twenties.
Canavan disease causes progressive brain atrophy. There is no cure, nor is there a standard course of treatment. Treatment is symptomatic and supportive.