Author: Tarannum Rehal
As vast as our knowledge of the various kinds of illnesses and diseases that affect the human body may be, science is constantly progressing to further increase our awareness and understanding of possible ailments. Similarly, as part of an assignment in my biochemistry course, I recently learned about Canavan’s Disease, an ailment I never heard of before, and would like to share my newfound knowledge with others as well!
Canavan’s disease is a rare but lethal neurological disorder belonging to a group of disorders known as leukodystrophies. This class of disorders affects the nervous system, which includes the brain, spinal cord, and peripheral nerves by deteriorating the white matter, known as myelin, present in neurons. Leukodystrophy, when broken down into its constituent words “leuko”
Typical neuron structure
and “dystrophy” can be understood as “white” and “destroy”. The myelin sheath serves as a protective and insulated coating around the nerves that promotes the efficient relay of nerve signals. Hence, with a disorder that deteriorates or breaks down the myelin white matter, as Canavan’s disease does, the ability of neurons to send and receive messages among one another is severely diminished. This process of myelin degradation is known as demyelination.
Canavan’s disease is an autosomal recessive disorder that affects males and females of all ethnic groups in equal parts but has been observed with the highest frequency in the Ashkenazi Jewish population with a carrier frequency of 1 in every 37 to 1 in every 57 individuals. It is most commonly observed during early infancy when the child is between 3 to 6 months of age. As an autosomal recessive disorder, both parents must be carriers that have passed down the mutated gene to their offspring, resulting in a 25% chance for their child to have the disorder. Canavan’s disease is caused by a mutation in the ASPA gene on chromosome 17 in humans, responsible for encoding an enzyme called aspartoacylase that results in the breakdown of N-acetylaspartic acid (NAA). NAA is a key chemical in the nervous system responsible for the generation and maintenance of the myelin sheath as well as the balance of fluids within neurons. So, with a mutation on the very gene responsible for the maintenance of white matter, NAA accumulates over time and interferes with the effective metabolism of NAA for myelin production thereby damaging the conduction of electrical signals transmitted by neurons necessary for normal bodily functions.
While a child may appear “normal” at birth, symptoms of Canavan’s disease start to make an appearance as soon as 3-6 months after birth. The most common symptoms include macrocephaly (abnormally large head), lack of muscle control that results in involuntary muscle spasms, partial paralysis, seizures, sleep disorders, reduced vision or partial blindness, and problems with speech (sloppy mouth movement). Another major symptom of Canavan’s disease is evident delays in reaching developmental milestones such as
Elevated Levels of NAA in Canavan's Disease
sitting independently and walking, or walking independently without the support of another. The severity of the symptoms varies from person to person and with the progression of the disease. The diagnosis for detecting the presence of Canavan’s disease is done through chromatography-mass spectrometry tests that are able to detect the increased levels of NAA in urine, blood, and cerebrospinal fluid samples in an individual.
Unfortunately, there is currently no cure or standard course of treatment for Canavan’s disease, however, some symptoms of this disorder can be managed with certain medications. For example, standard antiepileptic drugs can help with seizures, and involuntary muscle spasms with botulinum toxin injections. Physical therapy is also recommended to improve the affected individual’s posture to allow for the protection of their nasal/airway passage and reduce the risk of gastroesophageal acid reflux. The love and support of loved ones also significantly reduces strain on the mental health of the affected individual.
It is unfortunate that many diseases go unnoticed and unheard of until we know someone who is affected by it or until we get it assigned for a research assignment. As science continues to progress in its discoveries, I hope that one day there will be a cure for this genetic disorder as well as more awareness surrounding it.
"Typical Neuron Structure": https://userfilessecure.educatorpages.com/userfiles/RanchoBiology/Anatomy/
"Autosomal Recessive Inheritance":https://www.decodegenomics.com.pk/maple-syrup-urine-disease-msud/
"Elevated Levels of NAA in Canavan's Disease": https://www.casestacks.com/neuro/fellow-cases/case-17/