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Canavan disease, also called Canavan-Van Bogaert-Bertrand disease, aspartoacylase deficiency or aminoacylase 2 deficiency, is an autosomal recessive degenerative disorder that causes progressive damage to nerve cells in the brain. This disease is one of a group of genetic disorders called leukodystrophies.
Although Canavan disease may occur in any ethnic group, it affects persons of Eastern European Jewish ancestry more frequently. About 1/40 individuals of Eastern European (Ashkenazi) Jewish ancestry are carriers.
Canavan disease is inherited in an autosomal recessive fashion. When both parents are carriers, there is a 25% chance of having an affected child. Genetic counseling and genetic testing is recommended for families with two parental carriers.
Canavan disease is caused by a defective ASPA gene which is responsible for the production of the enzyme aspartoacylase. This enzyme breaks down the concentrated brain molecule N-acetyl aspartate. Decreased aspartoacylase activity prevents the normal breakdown of N-acetyl aspartate, and the lack of breakdown somehow interferes with growth of the myelin sheath of the nerve fibers in the brain. The myelin sheath is the fatty covering that surrounds nerve cells and acts as an insulator, which allows for efficient transmission of nerve impulses.
Symptoms of Canavan disease, which appear in early infancy and progress rapidly, may include mental retardation, loss of previously acquired motor skills, feeding difficulties, abnormal muscle tone (i.e., floppiness or stiffness), poor head control, and megalocephaly (abnormally enlarged head). Paralysis, blindness, or seizures may also occur.
There is no cure for Canavan disease, nor is there a standard course of treatment. Treatment is symptomatic and supportive.
Death usually occurs before age 4 without treatment. Some children may survive into their twenties via newer gene therapy treatments which have extended their life expectancy. In some cases, this helps to temporarily stop the progression of the disease.
Research involving triacetin supplementation has shown promise in a mouse model. Triacetin, which can be enzymatically cleaved to form acetate, enters the brain more readily than the negatively charged acetate.
A team of researchers headed by Paola Leone are currently at the University of Medicine and Dentistry of New Jersey, in Camden, New Jersey. The brain gene therapy is conducted at Cooper University Hospital. The procedure involves the insertion of six catheters into the brain that deliver a solution containing 600 billion to 900 billion engineered virus particles. The virus, a modified version of AAV, is designed to replace the aspartoacylase enzyme. Children treated with this procedure to date have shown marked improvements, including the growth of myelin with decreased levels of the n-acetyl-aspartate toxin.