Canavan disease (CD) is a neurodegenerative disease of the CNS that usually results in death. The disease leads to a spongy disintegration of the white matter of the brain and spinal cord.
The disease is divided into two forms: the most common, severe form begins in the neonatal period or in infancy and is associated with severe hypotonia, neurological disorders, leukodystrophy and severe retardation. The levels of N-acetyl-L-aspartic acid in the blood, urine and spinal fluid are greatly increased.
The less common, mild form is usually diagnosed in childhood and is characterized by a mild developmental delay, difficulties at school and language problems. The urinary N-acetyl-L-aspartic acid levels are slightly elevated.
Normally the first symptoms become noticeable between the 2nd and 4th month of life. Striking is the macrocephaly and hull hypotonia. As the disease progresses, symptoms such as spasticity, blindness, motor disorders, suction and drinking disorders, and hyperreflexia occur. End-stage patients suffer from spastic muscle paralysis, are no longer able to communicate, and ultimately die from respiratory paralysis.
Depending on the form, the survival time varies from a few days to decades, with patients of the severe form usually not exceeding the age of 10 years. In mild Canavan disease, patients have a normal life expectancy at best.
The cause is a mutation in the ASPA gene at the genome 17p13.3, which encodes the aspartoacylase enzyme. The enzyme activity is either low or absent, with multiple mutations identified. The rarity of the mild form is due to the fact that it is usually compound heterozygous for a mild and a severe mutation. The inheritance is autosomal recessive.
While the disease occurs worldwide, a large accumulation has been noted in the population of the Ashkenazim Jews. Especially two common mutations were identified here.