Canavan disease

Canavan disease is a rare inherited brain disorder in which damage to the white matter prevents normal development and movement. It occurs when harmful changes in the ASPA gene reduce the enzyme aspartoacylase, allowing a chemical called N-acetylaspartic acid to build up and block the formation of myelin, the protective coating around nerve fibers. The severity and specific features can vary considerably from person to person. Most babies show poor head control, weak muscle tone, and rapid head growth within the first months of life, although a few individuals do not develop symptoms until later childhood. Exact numbers are unknown, but the condition is uncommon worldwide and more frequent in certain ethnic groups.

Severity and symptoms vary widely between individuals. Most infants appear healthy at birth but soon develop neurological signs such as low muscle tone and feeding difficulties. Macrocephaly, or a rapidly enlarging head circumference, often becomes noticeable within the first year and may prompt neuroimaging. As the condition progresses, global developmental delay and significant cognitive impairment become evident, and many children are unable to achieve independent sitting or speech. Seizures, often reflected as abnormal EEG patterns or multifocal epileptiform discharges, can develop and range from infantile spasms to generalized tonic–clonic events. Vision pathways may also be affected, leading to nystagmus, optic atrophy, or reduced visual responses on evoked potential testing, while some children experience hearing impairment. Less consistently, children may alternate between hypotonia and later hypertonia or pyramidal signs, and episodes of reduced consciousness can occur during acute illness. Not all individuals experience all features, and severity varies considerably.

Canavan disease is caused by pathogenic variants in the ASPA gene. The ASPA gene provides instructions for making aspartoacylase, an enzyme that breaks down N-acetylaspartic acid in the brain. When both copies of ASPA carry harmful variants, enzyme activity is very low or absent, N-acetylaspartic acid accumulates, and myelin formation is disrupted, leading to the neurological manifestations of the condition. The disorder is inherited in an autosomal recessive pattern, meaning a child must receive one altered gene from each parent to be affected; carrier parents are typically healthy but have a 25 percent chance with each pregnancy of having an affected child. Canavan disease is more common when parents share a common ancestor because they are more likely to carry the same rare variant. Families often benefit from genetic counseling to understand carrier testing options and implications for future pregnancies.

Currently, management focuses on supportive care and symptom management tailored to each individual’s needs, as no disease-specific therapies have been approved. Foundational care includes nutritional support to address feeding difficulties, physiotherapy and occupational therapy to optimize motor abilities, and antiepileptic medications when seizures occur. Because the condition can involve multiple body systems, coordinated multidisciplinary care involving neurology, gastroenterology, pulmonology, nutrition, and rehabilitation specialists is recommended. Regular surveillance for vision and hearing problems, as well as monitoring of growth, swallowing safety, and respiratory function, helps detect complications early. Families may also explore investigational approaches such as gene-based therapies that are being studied in clinical trials, recognizing that eligibility and long-term benefits remain under investigation. Ongoing communication with the healthcare team ensures that emerging treatments and supportive resources are considered promptly.

Outcomes for Canavan disease depend on the age at onset and the severity of enzyme deficiency. Infants with the classic form typically experience profound developmental challenges and require long-term supportive care, while those with the very rare juvenile form may retain some independent skills into adolescence or adulthood. Medical complications such as feeding difficulties, aspiration, or refractory seizures can influence overall health, but proactive management and modern supportive therapies have improved quality of life for many affected individuals. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and specialty centers familiar with leukodystrophies for ongoing guidance, anticipatory care planning, and access to community resources.

Several clinical trials are currently investigating new treatments for Canavan disease, including gene replacement strategies aimed at restoring aspartoacylase activity. These studies reflect growing scientific interest in modifying the underlying biochemical defect rather than solely treating symptoms. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their care team about eligibility.