Canavan Disease 2011

Summary

Canavan's Disease is an inherited neurodegenerative disease. It was first generalized by Dr. Myrtelle Canavan in 1931 on the case of an infant deceased at the age of 16 months. While it is extremely rare in the general population, studies have shown Canavan's Disease to occur among eastern European Ashkenazi jews at a rate of one carrier in every 57 individuals. It is inherited in a Mendelian autosomal recessive fashion, resulting in a risk of 25% for a child of two carriers to be affected by the disease.

Phenotype

Symptoms usually appear in early infancy and progress rapidly, and with basic supportive care average life expectancy is about 18 months. In rare cases life expectancy can be as high as 33 years, although in this particular case the patient had degraded into a 'persistent vegetative state' at that age.

Symptoms are mainly neurologically in nature, with the most commonly observed ones being:

• Mental retardation
• Degradation of motor skills (especially head control)
• Abnormal muscle tone (muscles are either constantly too tense or too relaxed)
• Megalocephaly (abnormally enlarged head)

More rareley observed symptoms are:

• Seizures
• Blindness
• Paralysis

The neurodegeneration chiefly affects the cerebral white matter, which is made up by the axons connecting individual neurons. The disease attacks these axons by an as-of-yet unknown mechanism, although the compound [aspartate] appears to play a role in this process.

Biochemical disease mechanism

Much of the disease mechanism still lies in the dark; mutations causing the disease have been traced to a gene encoding for Aspartoacyclase http://www.ncbi.nlm.nih.gov/omim/608034, an enzyme that catalyzes the hydrolysis of N-Acetate aspartate into acetate and aspartate. It is made up of six exons in a gene called ASPA on the 17th chromosome, and its overall length is 313 amino acids.

Cross-Reference

• [[1]]
• [[2]]
• [Plus]
• [Bookshelf]
• [[3]]

Mutations

Reference sequence

Reference Sequence from UniProt

Neutral mutations

Coming soon

Disease causing mutations

Coming soon