Canavan disease is caused by the lack of a substance in the body called aspartoacylase (ASPA).  This substance is a type of protein (enzyme) normally found in the part of the brain where nerve impulses are sent to other parts of the brain and to the spinal cord.  ASPA breaks down a compound called NAA into two smaller compounds.  When ASPA is missing from the body, NAA builds up and causes brain damage, mental retardation, a large head size, tremors, and an inability to move muscles.  Canavan disease may also cause blindness (due to problems with nerves from the eye to the brain), feeding difficulties, poor weight gain, and problems with swallowing.

Normal Myelin Formation

Myelin Affected by Canavan

As illustrated above, a defective gene impairs the formation of myelin and allows the accumulation of a toxic compound. Canavan children are unable to hold up their heads, sit up, crawl, and most will never say a single word. As Canavan disease is progressive, the brain disintegrates into a spongy mass and even the most elemental signals cannot get through. These precious children gradually go blind, lose the ability to swallow, require feeding tubes, and can eventually fall into a vegetative state with no voluntary movement. Unless a cure is found, most Canavan children will die before their 10th birthday.

Who is at risk for Canavan disease?

Canavan disease may occur in any nationality and ethnic group, but it is most common in Jews of Eastern European descent (Ashkenazi Jews).  An estimated one in 40 Ashkenazi Jews is a carrier of Canavan disease.  Carriers do not have Canavan disease but are capable of passing it on to their children if the other parent is also a carrier. This carrier frequency makes Canavan disease almost as common in the Ashkenazi Jewish population as Tay-Sachs disease.

How do people get Canavan disease?

Canavan disease is an inherited condition, which means that it is passed from parents to their children.  An individual with Canavan disease has inherited two changed copies of the gene for ASPA, one from each parent.  Genes are our body's "instructions" on how to develop and function.  They are located on the structures in our cells called chromosomes.  Since we inherit one set of chromosomes from each of our parents, chromosomes, and the genes located on them, are in pairs.  If a person has one copy of the gene for ASPA functioning normally and the other copy not functioning, he or she is known as a carrier for Canavan disease.  Carriers do not show any symptoms of Canavan disease and usually have no health problems related to Canavan disease, but they are capable of passing the copy of the gene that does not function properly on to their children.

If two carriers for Canavan disease have a child together, each child has a:

• 1-in-4 (25%) chance of having Canavan disease,
• 2-in-4 (50%) chance of being a carrier,
• 1-in-4 (25%) chance of neither having Canavan disease nor being a carrier.
• Unaffected siblings of individuals with Canavan disease have a 2/3 (66%) chance of being carriers.

In this way, even two individuals who are carriers for Canavan disease have a 75% chance to have a child without the disease.  Because of this, families may not know that the gene that causes Canavan disease is running through their family, and individuals may not know that they are carriers of Canavan disease.

How is Canavan disease diagnosed?

Canavan disease can be diagnosed with a blood test.  A person with Canavan disease has no detectable amounts of ASPA, and the low level of this enzyme in a person's blood is characteristic of the disease.

The NAA that builds up in the body of a person with Canavan disease is excreted in the urine.  Individuals without Canavan disease have no detectable amounts of NAA in their urine.  The presence of NAA in the urine of an individual is sufficient to make the diagnosis of Canavan disease.

Prenatal diagnosis for Canavan disease is available using samples collected with procedures called chorionic villus sampling (CVS) or amniocentesis, which are performed early in pregnancy.

How are Canavan disease carriers identified?

The blood test also identifies carriers of Canavan disease.  In the Ashkenazi Jewish population, the detection rate for carriers using this blood test is 97%.  In other populations, this test can detect approximately 66% of carriers.

Is there a treatment or cure for Canavan disease?

The treatment of Canavan disease is aimed at alleviating the problems associated with the disease.  Seats with full support for the head are used, liquid diets or feeding tubes may be used since swallowing may become difficult, and medications to control or reduce seizures and irritability may be administered.

Recently, an experimental gene therapy project began for Canavan disease.  This study intends to transfer an unchanged copy of the gene to the brain cells of a patient.  This gene transfer has the potential to increase the amount of ASPA in the brain and thus allow breakdown of NAA.