What is Canavan Disease?
Canavan Disease is a rare autosomal recessive neurodegenerative disorder that usually affects infants within the first three to six months of their lives. It is a leukodystrophy that is distinguished by the degeneration of myelin sheaths, white matter, on axons which reside in the brain. Canavan disease is caused by a lack of aspartoacylase which regulates N-acetyl-l-aspartate (NAA) [1]. Elevated levels of NAA in the urine is how the disorder is diagnosed. Of those who develop the disease, the most common type of child is one of Ashkenazi Jewish descent. Most children with Canavan have the infantile, early-onset form. This form has more severe symptoms, and often results in death. It can also be developed slightly later in childhood, and this juvenile form is more manageable [2].
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Symptoms and Treatment
Early onset Canavan disease develops within the first 3-6 months of a child's life. There are many symptoms of the disease such as low of muscle tone, macrocephaly (increased head size), blindness, hearing-loss, seizures, difficulty with feeding, and developmental delays. Juvenile Canavan disease causes mild delays in speech and motor development [2].
Treatment is focused on dealing with the symptoms of the disease because there is no cure for the disease itself. Treatments used to moderate the symptoms include: medication for seizures, speech or physical therapy, and gastronomy for proper nutrition [3].
How is ASPA gene involved?
The ASPA gene is located on chromosome 17, and it is responsible for synthesizing aspartoacylase. Aspartoacylase breaks down NAA into acetate and aspartate by hydrolysis [3]. Mutations in the ASPA gene lead to a deficiency in aspartoacylase, and NAA is no longer regulated. NAA levels are elevated in the brain, and the deficiency leads to the deterioration of myelin. This is due to the lowered levels of hydrolyzed acetate, which plays a role in the myelin’s synthesis [1].
This is a representation of where ASPA is located in chromosome 17.
Gap in Knowledge
The function of ASPA in the maintenance myelin production during early development is unclear.
References
1. Matalon, D., Michals-Matalon, K., & Matalon, R. (2020). Chapter 66 - Canavan disease. Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease (Sixth Edition), Academic Press, 909-916. https://doi.org/10.1016/B978-0-12-813955-4.00066-0
2. Matalon, R., Delgado, L., & Michals-Matalon, K. (1999). Canavan Disease. In M. P. Adam (Eds.) et. al., GeneReviews®. University of Washington, Seattle.
3. Pleasure, D., Guo, F., Chechneva, O., Bannerman, P., McDonough, J., Burns, T., Wang, Y., & Hull, V. (2020). Pathophysiology and Treatment of Canavan Disease. Neurochemical research, 45(3), 561–565. https://doi.org/10.1007/s11064-018-2693-6
4. Dembic, M., Andersen, H. S., Bastin, J., Doktor, T. K., Corydon, T. J., Sass, J. O., Lopes Costa, A., Djouadi, F., & Andresen, B. S. (2019). Next generation sequencing of RNA reveals novel targets of resveratrol with possible implications for Canavan disease. Molecular genetics and metabolism, 126(1), 64–76. https://doi.org/10.1016/j.ymgme.2018.10.004
2. Matalon, R., Delgado, L., & Michals-Matalon, K. (1999). Canavan Disease. In M. P. Adam (Eds.) et. al., GeneReviews®. University of Washington, Seattle.
3. Pleasure, D., Guo, F., Chechneva, O., Bannerman, P., McDonough, J., Burns, T., Wang, Y., & Hull, V. (2020). Pathophysiology and Treatment of Canavan Disease. Neurochemical research, 45(3), 561–565. https://doi.org/10.1007/s11064-018-2693-6
4. Dembic, M., Andersen, H. S., Bastin, J., Doktor, T. K., Corydon, T. J., Sass, J. O., Lopes Costa, A., Djouadi, F., & Andresen, B. S. (2019). Next generation sequencing of RNA reveals novel targets of resveratrol with possible implications for Canavan disease. Molecular genetics and metabolism, 126(1), 64–76. https://doi.org/10.1016/j.ymgme.2018.10.004
Foundations and Organizations