Canavan Disease (CD)

Canavan disease is an autosomal genetic, progressive neurodegenerative disorder that causes the white matter (myelin) to break down (demyelination) and in which the brain degenerates into spongy tissue riddled with microscopic fluid-filled spaces. The outcome is a shortened life span as a result of the damage caused to the Central Nervous System (CNS).

What causes Canavan Disease?

A mutated or defective ASPA (aspartoacylase) gene which is located on Chromosome 17 (17p13.3) which encodes the aspartoacylase enzyme This enzyme’s function is to break down a compound called N-acetyl-L-aspartic acid (NAA) into aspartic acid (an amino acid that is a building block of many proteins) and another molecule called acetic acid.

This mutation causes a deficiency in enzyme activity, leading to a build up of the chemical N-acetylaspartic acid (NAA) in the cells of the body. This molecule is also thought to be involved in the removal of water from certain types of brain cells, as well as in the formation of myelin lipids. Recent research has indicated that the cells in the brain responsible for making myelin sheaths, known as oligodendrocytes, cannot properly complete this critical developmental task. Myelin sheaths are the fatty covering that act as insulators around the axons as well as providing nutritional support for neurons. In Canavan disease, many oligodendrocytes do not mature and instead die, leaving these axons vulnerable and unable to properly function.

Who gets Canavan Disease?

While this condition occurs in people of all ethnic backgrounds, it is most common in people of Ashkenazi Jewish heritage. It is more frequent among Ashkenazi Jews from eastern Poland, Lithuania, and western Russia, and among Saudi Arabians. Studies suggest that this disorder affects 1 in 6,400 to 13,500 people in the Ashkenazi Jewish population. The incidence in other populations is unknown.

It is estimated that 1 in 40 – 1 in 58 in the Ashkenazi Jewish heritage is a carrier of Canavan disease. A carrier will show no symptoms of the disease and may have no known family history of the disease, but can pass it along to his or her children. As it is Autosomal in its inheritance two carrier parents have a 1 in 4 chance–with each pregnancy–of having a child affected with Canavan disease.

Prognosis:

The prognosis for Canavan disease is poor. Death usually occurs before age 10, although some children may survive into their teens and twenties.

Symptoms of CD

Symptoms of Canavan disease usually appear in the first 3 to 6 months of life and progress rapidly. Please remember that not all affected children have the same symptoms and at the same severity. Symptoms include lack of motor development, abnormal muscle tone with decreased muscle tone (Hypotonia) particularly in the neck region. Legs may be abnormally straight (Hyperextension). The muscles in the arms may tend to be flexed. They may have an abnormally large head (Macrocephaly) Paralysis, blindness, or hearing loss may also occur. Children are characteristically quiet and apathetic and do not thrive. Feeding and swallowing difficulties may occur with nasal regurgitation and reflux with vomiting. Seizures across the entire spectrum may occur as with all Leukodystrophies.

How do we diagnose CD?

CT scan or MRI scan: To look for the degeneration of the white matter of the brain

Urine/blood/cerebrospinal fluid test: To look for increased N-acetyl-L-aspartate (NAA) in these fluids, suggesting a deficiency in the enzyme aspartoacylase

Genetic testing for aspartoacylase gene mutations: Since the genetic basis of the disease is known to be a defect in the gene encoding aspartoacylase, the DNA of the child can be tested to look for mutations in this gene. Laboratory tests can identify a lack of ASA in skin cells or elevated levels of N-acetylaspartic acid (NAA) in urine. Genetic testing looks for four common mutations in the gene for Canavan disease, two of which are mainly found in the Ashkenazi Jewish population. There at least 55 known mutations on the ASPA gene.

Is prenatal diagnosis available?

Testing is available to those with an affected child or to couples found to be at risk by carrier testing. Prenatal genetic diagnosis (PGD) is possible by this method, and genetic counselling is recommended for prospective parents who have a family history of Canavan Disease. Parents can also be screened to see if they are carriers of the disease.

Treatments for CD:

Treatment is symptomatic and supportive. Currently there is no effective treatment or cure for this condition. We do those things that help maximize nutrition, fight infection and protect breathing and maintain bodily hygiene.

What research is being done?

Gene Replacement Therapy, Stem Cell Therapy and Pharmacological approaches are currently being trialled and encouraging results have been obtained using these strategies.

What other names do people use for Canavan disease?

ACY2 deficiency
Aminoacylase 2 deficiency
ASPA deficiency
Aspartoacylase deficiency
Asp deficiency
Canavan-Van Bogaert-Bertrand disease
Leukodystrophy, spongiform
Spongy degeneration of central nervous system
Spongy degeneration of the brain
Spongy degeneration of white matter in infancy
Van Bogaert-Bertrand syndrome
Von Bogaert-Bertrand disease