What is Canavan Disease?
Canavan disease is a rare genetic neurological disorder characterized by the spongy degeneration of the white matter in the brain. Affected infants may appear normal at birth, but usually develop symptoms between 3-6 months of age. Symptoms may include an abnormally large head (macrocephaly), lack of head control, severely diminished muscle tone resulting in “floppiness,” and delays in reaching developmental milestones such as independent sitting and walking. Most affected children develop life-threatening complications by 10 years of age. Canavan disease occurs because of mutations in the aspartoacylase (ASPA) gene that affects the breakdown (metabolism) of the N-acetylaspartic acid (NNA). It is inherited as an autosomal recessive condition.
Canavan disease belongs to a group of disorders known as the leukodystrophies. The leukodystrophies are a group of rare, progressive, metabolic, genetic disorders that can affect the brain, spinal cord, and often the nerves outside the central nervous system (peripheral nerves). Each type of leukodystrophy is caused by an abnormality affecting a specific gene that results in the abnormal development of one of at least 10 different chemicals that make up the white matter of the brain. The white matter is a tissue composed of nerve fibers. Many of these nerve fibers are covered by a collection of fats (lipids) and proteins known as myelin. Myelin, which collectively may be referred to as the myelin sheath, protects the nerve fibers, acts as an insulator, and increases the speed of transmission of nerve signals. Each type of leukodystrophy affects a different part of the myelin sheath, leading a range of different neurological problems.
Canavan disease affects males and females in equal numbers. It affects all ethnic groups but occurs with greater frequency in individuals of Ashkenazi Jewish descent. In this population, the carrier frequency is estimated to be as high as one in 40-58 people. The risk for an affected child born to Ashkenazi Jewish parents is between 1 and 6,400 and 1 in 13,456. The carrier frequency in other populations is not known but is most likely far lower. The overall incidence of Canavan disease in the general population is unknown.