Canavan has been classified as a leukodystrophy, a group of more than 15 rare genetic disorders that cause progressive degeneration of the white matter of the brain due to imperfect growth or destruction of the myelin sheath, the fatty covering that insulates nerve fibers in the brain and spinal cord and promotes rapid transmission of nerve impulses. Without myelin, nerve cells cease to function and eventually die. As myelin deteriorates in leukodystrophies such as Canavan Disease, nervous system function is impaired. The leukodystrophies are often referred to as “demyelinating” diseases.
Canavan disease, one of the most common cerebral degenerative diseases of infancy, is a gene-linked, neurological birth disorder in which the brain degenerates into spongy tissue riddled with microscopic fluid-filled spaces. The disease is caused by a mutation in the gene for an enzyme called aspartoacylase, which acts to break down the concentrated brain chemical known as N-acetyl-aspartate. Unlike most leukodystrophies, both grey and white matter are severely affected in infants with Canavan disease.
Symptoms of Canavan disease usually appear in the first 3 to 6 months of life and progress rapidly. Symptoms include lack of motor development, feeding difficulties, abnormal muscle tone (weakness or stiffness) and an abnormally large, poorly controlled head. Paralysis, blindness and hearing loss may also occur. Children are characteristically quiet and apathetic. Although Canavan disease may occur in any ethnic group, it is more frequent among Ashkenazi Jews from eastern Poland, Lithuania and western Russia, and among Saudi Arabians. Canavan disease can be identified by a simple prenatal blood test that screens for the missing enzyme or for mutations in the gene that controls aspartoacylase. Both parents must be carriers of the defective gene in order to have an affected child. When both parents are found to carry the Canavan gene mutation, there is a one in four (25%) chance with each pregnancy that the child will be affected with Canavan disease.
The prognosis for Canavan disease is poor. Death usually occurs before age 10, although some children may survive into their teens and twenties.
The most common leukodystrophies include Canavan disease, Krabbe disease, metachromatic Leukodystrophy (MLD), Childhood Ataxia with Central Nervous System Hypomyelination (CACH), Alexander disease and Refsum disease.