Introduction

Canavan disease, also known as Canavan-Van-Bogaert-Bertrand disease, is a rare, progressive, and fatal hereditary neurological disorder that begins in infancy. Canavan disease affects the brain’s white matter, which is responsible for transmitting signals between different parts of the brain and the rest of the body.¹ It is part of a group of genetic disorders called leukodystrophies, and it is caused by a deficiency in the enzyme aspartoacylase, leading to the accumulation of N-acetylaspartic acid (NAA) in the brain. 

Early and accurate diagnosis of Canavan disease is crucial. Identifying this condition promptly allows families and healthcare providers to plan for care, access support services, and consider available treatment options. Early diagnosis also helps families understand the genetic risk for future offspring and make informed decisions. 

Who does it affect?

Infants and young children are most commonly affected. Most infants appear healthy after birth, but within 2 to 6 months, obvious symptoms like motor development typically appear.² The infant may not be able to move around, control their head movements, or support themselves. Hypotonia (decreased muscle tone) is a common feature and is associated with macrocephaly (large head circumference).

The disease is inherited in an autosomal recessive pattern, which means that both parents must carry a mutation in the ASPA gene for a child to be affected by Canavan disease.

Common symptoms

Canavan disease is often not obvious at birth. In many cases, signs of the condition begin to show within the first few months of the infant’s life. Some common symptoms include:

• Decreased muscle tone (hypotonia)
• Poor visual tracking
• Involuntary eye movements
• Delays in reaching developmental milestones (such as crawling or walking)
• Difficulty with feeding and swallowing
• Abnormally large size (macrocephaly)
• Seizures
• Vision and hearing problems

Canavan disease is a serious condition, but understanding it can help families seek the right care and explore available support. 

Why is diagnosis important?

Early intervention and support

Early diagnosis of Canavan disease allows families and healthcare teams to begin supportive therapies as soon as possible. Starting interventions early - such as physical, occupational and speech therapy can help maximise a child’s ability and improve quality of life. Early detection also means that families can access specialised resources, support groups, and expert care tailored to the unique challenges of Canavan disease. 

Planning for care and management

A confirmed diagnosis helps families and doctors create a personalised and unique care plan. This may include regular monitoring, diet changes, seizure management, and therapies to address the delays in development. This allows a team of specialists, which includes neurologists, genetic counsellors and therapists, to coordinate care and anticipate any future needs. 

Diagnosis also provides important information for family planning. Genetic counselling can help parents understand the risks involved when planning for future children and explore options such as carrier testing. 

Early and accurate diagnosis is essential for ensuring that children with Canavan disease receive the best possible care and support from the beginning. 

Steps in diagnosing canavan disease 

Medical history and physical exam

• Family History:

Doctors begin by asking about any family history of genetic conditions, especially if there are known cases of Canavan disease or related disorders. This helps identify children who may be at higher risk. 

• Observing Symptoms:

A physical exam is performed to look for signs such as developmental delays, hypotonia (poor muscle tone), macrocephaly (unusually large head), feeding difficulties and other neurological symptoms. These are early signs which often prompt further testing. 

Laboratory tests

• Urine Test:

This test checks for high levels of a chemical called N-acetylaspartic acid (NAA) in the urine.³ Elevated NAA is a hallmark of Canavan disease because the body is unable to break it down effectively. 

A urine test is simple and non-invasive, which is often used as an initial screening tool if Canavan disease is suspected based on the symptoms. A genetic test for the ASPA gene may be done to further confirm the diagnosis of Canavan disease.

• Blood Test:

A blood test may be used to search for mutations in the ASPA gene, which causes Canavan disease. It may also be used to measure NAA levels. Blood testing helps to confirm the diagnosis by identifying genetic changes linked to the disease. 

Genetic testing

Genetic testing provides a more comprehensive look for mutations in the ASPA gene. This can confirm the diagnosis in the child and is especially important if the urine test is positive.

Genetic testing is recommended for family members to determine if they are carriers of the ASPA gene mutation. This information is crucial for family planning and understanding the risk for future offspring. 

These steps ensure an accurate diagnosis of Canavan disease. Early detection enables families to access the appropriate care and support. 

Imaging tests

• Magnetic Resonance Imaging (MRI)

MRI is the main imaging test used to help diagnose Canavan disease. It is a type of scan that takes detailed pictures of the brain, allowing doctors to see if there are any unusual changes in how the brain looks or develops.

Children diagnosed with Canavan disease often have specific changes in the brain’s white matter on MRI. These areas often appear as regions of abnormal signal or swelling (increased water content) in the white matter, especially in regions important for motor function and development.⁴ MRI is a safe and painless test which does not use radiation and is non-invasive. Sedation may be needed for infants and young children to help them remain still during the scan. 

• CT Scans

Computed Tomography (CT) scans may also detect changes in the brain, but they are used less frequently for Canavan disease as it is less sensitive than MRI for white matter changes and involve exposure to a small amount of radiation. 

Prenatal testing

If both parents are known carriers of the gene that causes Canavan disease, there is a 1 in 4 chance that their baby could be affected. In such cases, prenatal testing can help determine if the baby has inherited the condition before birth and make informed decisions about pregnancy and early care. 

Common testing methods

• Chorionic Villus Sampling (CVS):

Usually done between 10 to 12 weeks of pregnancy. A small sample of tissue from the placenta is tested for ASPA gene mutations.⁵

• Amniocentesis:

Usually done between 14 to 18 weeks of pregnancy. A small sample of amniotic fluid is taken from the fetus and tested for high levels of N-acetylaspartic acid (NAA).⁶

Why prenatal diagnosis matters

• Helps parents prepare for the possibility of their child being diagnosed with Canavan disease
• Allows for informed decision-making, genetic counselling and family planning
• Early diagnosis enables prompt access to care and resources after birth

These tests are optional and can be discussed with a doctor or genetic counsellor, who can help guide families through the decision-making process.

What happens after diagnosis

Getting a diagnosis of Canavan disease can be overwhelming for any family. But once the condition is confirmed, a doctor or genetic counsellor can help families understand the nature of the condition, causes and likely course of the disease. 

Referral to specialists

Doctors will usually refer the child to one or more specialists, including neurologists, therapists, nutritionists and social workers, to create a management plan tailored to the patient’s needs. Areas to focus include:

• Symptom management, such as controlling seizures and addressing feeding or swallowing difficulties
• Regular assessments for growth, mobility and developmental progress
• Preventing complications like respiratory infections and joint stiffness
• Physical, occupational and speech therapy to promote development, communication and comfort

This approach helps ensure that children with Canavan disease receive optimal care and that families are supported throughout the journey. 

Summary

Canavan disease is a rare but serious condition that affects the brain and the development of children. While symptoms may not appear right away, signs like poor muscle tone, delayed milestones, and an unusually large head often prompt doctors to investigate further. 

Early diagnosis of Canavan disease is crucial. Although there is no cure, identifying the condition as soon as possible gives children the best chance to benefit from supportive therapies and specialised care. Early intervention can help manage symptoms, improve quality of life and guide families with the resources they need for ongoing support and planning.