Canavan disease Health Article

Definition

Canavan disease, which results when the body produces less than normal amounts of a protein called aspartoacylase, is a fatal inherited disorder characterized by progressive damage to the brain and nervous system.

Description

Canavan disease is named after Dr. Myrtelle Canavan who described a patient with the symptoms of Canavan disease but mistakenly diagnosed this patient with Schilder's disease. It was not until 1949, that Canavan disease was recognized as a unique genetic disease by Van Bogaert and Betrand. The credit went to Dr. Canavan, however, whose initial description of the disease dominated the medical literature.

Canavan disease, which is also called aspartoacylase deficiency, spongy degeneration of the brain, and infantile spongy degeneration, results from a deficiency of the enzyme aspartoacylase. This deficiency ultimately results in progressive damage to the brain and nervous system and causes mental retardation, seizures, tremors, muscle weakness, blindness and an increase in head size. Although most people with Canavan disease die in their teens, some die in childhood and some may live into their twenties and thirties.

Canavan disease is sometimes called spongy degeneration of the brain since it is characterized by a sponginess or swelling of the brain cells and a destruction of the white matter of the brain. Canavan disease is an autosomal recessive genetic condition that is found in all ethnic groups, but is most common in people of Ashkenazi (Eastern European) Jewish descent.

Genetic profile

Canavan disease is an autosomal recessive genetic disease. A person with Canavan disease has changes (mutations) in both of the genes responsible for producing the enzyme aspartoacylase and has inherited one changed gene from his or her mother and one changed gene from his or her father. The aspartoacylase gene is called ASPA and is located on chromosome number 17. There are a number of different types of changes in the ASPA gene that can cause Canavan disease, although there are three common gene changes. When the ASPA gene is changed it does not produce any aspartoacylase or produces reduced levels of this enzyme. The amount of aspartoacylase produced depends on the type of gene alteration. Reduced production of aspartoacylase results in lower than normal amounts of this enzyme in the brain and nervous system. Aspartoacylase is responsible for breaking down a substance called N-acetylaspartic acid (NAA). When the body produces decreased levels of aspartoacylase, a build-up of NAA results. This results in the destruction of the white matter of the brain and nervous system and causes the symptoms of Canavan disease.

Parents who have a child with Canavan disease are called carriers, since they each possess one changed ASPA gene and one unchanged ASPA gene. Carriers usually do not have any symptoms since they have one unchanged gene that can produce enough aspartoacylase to prevent the build-up of NAA. Each child born to parents who are both carriers for Canavan disease has a 25% chance of having Canavan disease, a 50% chance of being a carrier and a 25% chance of being neither a carrier nor affected with Canavan disease.

Demographics

Although Canavan disease is found in people of all ethnicities, it is most common in Ashkenazi Jewish individuals. Approximately one in 40 Ashkenazi Jewish individuals are carriers for Canavan disease and approximately one in 6,400 Ashkenazi Jewish people are born with Canavan disease.

Signs and symptoms

Most infants with Canavan disease appear normal for the first month of life. The onset of symptoms, such as a lack of head control and poor muscle tone, usually begins by two to three months of age, although some may have an onset of the disease in later childhood. Children with Canavan disease usually experience sleep disturbances, irritability, and swallowing and feeding difficulties after the first or second year of life. In many cases, irritability resolves by the third year. As the child with Canavan disease grows older there is a deterioration of mental and physical functioning. The speed at which this deterioration occurs will vary for each affected person. Children with Canavan disease are mentally retarded and most will never be able to sit, stand, walk or talk, although they may learn to laugh and smile and reach for objects. People with Canavan disease have increasing difficulties in controlling their muscles. Initially they have poor muscle tone but eventually their muscles become stiff and difficult to move and may exhibit spasms. Canavan disease can cause vision problems and some people with Canavan disease may eventually become blind. People with Canavan disease typically have disproportionately large heads and may experience seizures.