Canavan disease genetics and symptoms

Canavan disease
Canavan disease is a rare inherited genetic disorder that occurs in mainly Central and Eastern European Jewish populations. One person in 6,400 Central Europeans and one in 13,500 Eastern European populations get diagnosed with Canavan disease, which affects the ability of neurons to send messages to the brain. It is thought that 1 in every 40 Ashkenazi Jews are carriers for Canavan disease, so usually will not have any of Canavan disease’s symptoms. However, there is such a good screening program for the Jewish population for Canavan disease that most of the children now born with Canavan disease have no known Jewish heritage. Canavan disease is part of a group of genetic disorders which are called leukodystrophies, which affect the myelin sheath which protects the nerves and enable efficient transmission of nerve impulses.

More general information about Canavan disease can be found at:

www.ghr.nlm.nih.gov/condition/canavan-disease

www.canavanfoundation.org/about_canavan_disease

www.omim.org/entry/271900

Genetics behind Canavan disease

Mutations in the ASPA gene cause Canavan disease. This gene gives instructions for making the enzyme, aspartoacylase, which normally breaks down a compound which is abbreviated to NAA. NAA is mainly present in the neurons (specialised cells which transmit nerve impulses) of the brain and its function is unknown. Therefore if there is a mutation in the ASPA gene, aspartoacylase cannot function normally and cannot break down NAA. An excess of NAA in the brain creates a chemical imbalance which interferes with the formation of the myelin sheath (the protective layer over nerve cells), which is normally carried out by oligodendrocyte cells, as well as causing death of the oligodendrocytes. Without their protective coating, nerves malfunction, this disrupts the brain’s normal development. When the brain’s normal development is disrupted symptoms of Canavan disease occur.

More information on the genetics of Canavan disease can be found at:

www.ghr.nlm.nih.gov/condition/canavan-disease

http://www.medicinenet.com/canavan_disease/page2.htm#what_are_the_symptoms_of_canavan_disease

Canavan disease is inherited when there are mutations in both copies of the ASPA genes in each cell of an individual inherited from the mother and the father (an autosomal recessive condition). However, the mother and father typically will not show any symptoms of Canavan disease as they are just carriers of the disease.

More information on how Canavan disease is inherited can be found at:

www.ghr.nlm.nih.gov/condition/canavan-disease

Symptoms of Canavan disease

There are two forms of Canavan disease. The first form is neonatal/infantile Canavan disease which is the most common and severe of the two forms. Life expectancy for this form of Canavan disease is very short and infants with the disorder usually live only into childhood and not past the age of ten. Symptoms of Canavan disease usually develop in babies between three and nine months old and then progress quickly.

Symptoms of neonatal/infantile Canavan disease include: