Canavan disease: Year of the Zebra

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Canavan disease is a rare form of leukodystrophy, a group of conditions that result in the degeneration of white matter in the brain, which is the part of the cerebral cortex filled with myelinated axons.
An axon is the part of a nerve cell that conducts neural impulses, allowing neural signals to travel throughout the nervous system.
Myelin refers to the fatty coating around axons which helps insulate the axon to make neural impulses travel quickly and efficiently.
Loss of myelin, or demyelination, makes travel for neural impulses difficult, ultimately leading to a variety of sensory, motor, and cognitive problems.
Specifically, Canavan disease results from a mutation in the ASPA gene, which causes a deficiency in the enzyme aspartoacylase.
This enzyme breaks down a molecule called N-acetyl-L-aspartic acid, or NAA, which is mainly found in specialized cells that produce myelin.
Impaired breakdown of NAA and its accumulation in the brain is thought to interfere with myelin production, but the exact mechanism why this happens is not well understood.
Mutations in the ASPA gene are inherited in an autosomal recessive pattern, meaning an individual must inherit two copies of the mutated gene, one from each parent, to develop the condition.
In Canavan disease, symptoms vary based on the age of onset. Children with the early-onset, or infantile, form typically have usual psychomotor development for the first few months of life.
Symptoms begin by 3 to 5 months of age, and include a larger head size; low muscle tone; and delayed development of motor milestones, like rolling over, holding their head upright, and sitting up without support.
Other common features include difficulty tracking objects with the eyes, blindness, and decreased sucking ability. Over time, the disease progresses to cause feeding and swallowing difficulties, seizures, and sleep disturbances.
There is also late-onset Canavan disease, known as the juvenile form, which begins after five years of age and is less severe.
It is characterized by spasticity, or abnormal muscle stiffness; cerebellar dysfunction, like vertigo or dizziness; nystagmus, or irregular eye movements; and unsteady gait.
There can also be delayed development of speech and motor skills, however, symptoms may be so mild that the disease goes undiagnosed.
Individuals with the infantile form of Canavan disease typically have a shortened life expectancy, with death occurring around ten years of age on average; though some individuals may live into their teens and early twenties.
Individuals with the juvenile form typically have a normal life expectancy.Diagnosis of Canavan disease is suspected based on the presence of clinical symptoms and lab tests showing elevated levels of NAA in the urine.
Additional tests may include a brain MRI that can help visualize degeneration of the white matter, as well as an electroencephalogram, or EEG, which monitors the brain’s activity.
Finally, genetic testing showing mutations on the ASPA gene can confirm the diagnosis.Unfortunately, there is currently no cure for Canavan disease, and treatment focuses on managing symptoms.
Physical therapy may be helpful for motor difficulties, and symptoms like seizures can be managed with antiepileptic medications.
Artificial feeding may be used to maintain adequate nutrition when there is difficulty swallowing. Finally, clinical trials have shown potential in treating Canavan disease with gene therapy, which aims to replace the mutated ASPA gene with a functional one.Alright, as a quick recap… Canavan disease is a rare neurodegenerative disorder that causes degeneration of white matter in the brain due to genetic mutations in an enzyme necessary to break down NAA.
Symptoms can include a large head size, low muscle tone, developmental delays, and seizures. There is no cure for Canavan disease, so treatment focuses on managing symptoms.