Canavan Disease affects both males and females, and all ethnic groups. However, the disease is much more prevalent in individuals of Ashkenazi (German & Eastern European) Jewish descent. 1 in 40-58 individuals in this population carry at least one defective copy of the gene associated with Canavan Disease. The overall carrier frequency and incidence of the disease in the general population is unknown.

Individuals with Canavan Disease have a mutation in the gene for an enzyme called aspartoacylase (ASPA), which is responsible for breaking down N-acetylaspartic acid (NAA). NAA is a compound that is believed to play a key role in the maintenance of the brain’s white matter. As a result of NAA not being broken down efficiently by ASPA, NAA starts to accumulate in brain tissue and the high levels of this compound cause damage to the white matter. 

Canavan Disease belongs to a group of disorders called Leukodystrophies, which are rare, progressive, metabolic, genetic disorders that can affect the brain, spinal cord and nerves outside the central nervous system (peripheral nerves). Each type of leukodystrophy is the result of a specific gene abnormality that causes abnormal development of one of at least 10 different chemicals that make up the brain’s white matter.

The gene mutation is inherited as an autosomal recessive trait, meaning that a dysfunctional copy of the gene needs to be inherited from both parents. The defective gene has been associated with chromosome 17 (17pter-p13). 

Symptoms and progression of Canavan Disease can vary, but the following are common symptoms and signs:

• Extremely poor head control

• Macrocephaly (large head)

• Severely diminished muscle tone (hypotonia)

• Difficulty swallowing, which in turn leads to feeding difficulties

• Unresponsiveness, fatigue or irritability

• Delays in significant developmental milestones, such as sitting or walking independently ( most affected infants never walk independently)

• Seizures

• Sleeping problems

• Nasal regurgitation (when food and liquids move up the nose with swallowing)

• Acid reflux

• Deterioration of the nerves in the eyes resulting in optic atrophy and reduced visual responsiveness.

• Hearing loss may occur

As affected infants age, hypotonia can progress into muscle spasms, slow, stiff leg movements, and can even worsen to paralysis. The severity and rate of disease progression vary, and the life-threatening complications associated with the disease may develop in infancy or later in teenage years in some cases. 

Affected infants are suspected to have Canavan Disease with the characteristic signs and symptoms as listed above. A diagnosis may be confirmed through clinical assessment, detailed patient history and through a range of specialized tests. 

Prenatal diagnosis is also available through amniocentesis in which the level of NAA in the amniotic fluid, fluid surrounding the developing fetus, is measured. This is measured at 16-18 weeks of gestation. If both parents are known to have ASPA gene mutations, prenatal testing is available using chorionic villus sampling which involves taking a sample of placental cells at 10-12 weeks gestation.

Specialized tests that may be used to confirm diagnosis include:

• Gas chromatography-mass spectrometry, a device used to detect high levels of NAA in the urine.

• Blood and cerebrospinal fluid samples may also be collected as these can also detect elevated levels of NAA.

• Connective tissue cell samples from the skin (cultured fibroblasts) may also be collected to reveal ASPA deficiency. 

Unfortunately, there is no cure or specific treatment for the disease. However, symptoms can be managed through professional support and supportive care. Physical therapy and early intervention may be helpful in improving posture or communication skills. Feeding tubes may be used for any swallowing problems, and anti-seizure medications may be used to treat associated seizures. 

Although the prognosis for Canavan Disease is poor and individuals typically do not live beyond the age of 10, some children may live into their teens and twenties.

Canavan Foundation. About Canavan Disease. 2021. Available from: https://www.canavanfoundation.org/about_canavan_disease#:~:text=Canavan%20disease%20is%20a%20progressive,proper%20transmission%20of%20nerve%20signals. 

National Institute of Neurological Disorders and Stroke. Canavan Disease Information Page. 2019. Available from: https://www.ninds.nih.gov/Disorders/All-Disorders/Canavan-Disease-Information-Page 

National Organization for Rare Disorders. Canavan Disease. 2015. Available from: https://rarediseases.org/rare-diseases/canavan-disease/ 

National Tay-Sachs & Allied Diseases Association (NTSAD). Canavan Disease. 2016. Available from: https://www.ntsad.org/index.php/canavan