Introduction

We’ve got the answers you’re looking for. We understand how important it is to recognise the signs and symptoms of Canavan disease in infants. With clear, research-based information, you’ll know exactly what these symptoms are and why early detection matters.

Canavan disease is a rare neurodegenerative disease, belonging to a group of genetic disorders known as leukodystrophies, which affect the white matter of the brain, spinal cord and nerves outside the CNS. This disease occurs due to mutations in the ASPA gene, which makes an enzyme that breaks down the compound NAA in the brain. The lack of the enzyme’s ability to break it down causes an increase in the levels of NAA in the brain and body fluids,¹ as well as damaging the white matter of the brain, with scans showing the brain having a lack of myelin.² This results in symptoms such as developmental delay, macrocephaly and seizures.⁴ This disease is an autosomal recessive condition, mainly affecting Ashkenazi Jewish populations.³ Thus, understanding the signs and symptoms of this disease is important to prevent misdiagnosis in the early stages, which could worsen the child’s growth and development. Early detection is important for prognosis, as well as family planning, ensuring the child is given the right support and care.

When is the onset of this disease?

At birth, affected people usually tend to be normal. However, developmental problems usually start at around 3 to 5 months, such as infants not having appropriate motor skills, such as the ability to control head movements or to sit without support. There is a gradual neurological decline as brain myelin fails to develop properly, resulting in axonal dysfunction and a disruption of information processing between the areas of the brain.⁵

What are early neurological signs? 

One of the main signs and symptoms of Canavan disease is delayed milestones, such as motor and developmental delays, which can include:⁶

• Inability to sit, stand, walk, or roll over   
• Poor head control due to weak muscle tone or floppiness, which can progress into spasticity, leading to further motor challenges. For example, there can be uncontrolled stiffening of the limbs or paralysis
• Progressive growth of the head, known as macrocephaly 

Are there any feeding and behavioural signs present?

Infants with Canavan disease may also have difficulties in feeding and swallowing, known as dysphagia, and so would need a gastrostomy tube to help with feeding. There may also be acid from the stomach backing into the oesophagus, causing further issues such as choking and vomiting.

In some children, sleep disturbances and irritability are also seen. Excessive crying or sleepiness and reduced engagement with surroundings can also occur as the disease progresses.

Are there any visual and auditory signs seen?

Infants may have poor visual symptoms such as:⁶

• Trouble focusing and tracking objects
• Limited or absent eye contact
• Seemingly staring into space
• Damage to the optic nerve, optic atrophy and retinal degeneration can cause reduced vision
• Nystagmus, which is rapid and involuntary eye movements developing in infancy

Auditory symptoms are rare but may be seen as a lack of reaction to sounds or voices.

What are other physical signs in patients?

Seizures may not be frequent during the first year, but can develop in half of patients over time, such as tonic clonic spasms and infantile spasms, as well as involuntary muscle contractions and stiffness. In terms of respiratory irregularities, shallow breathing or apnoea episodes can also be seen in some.

How is the diagnosis made?

Acknowledgement of the physical signs as well as family history can lead to a diagnosis of this disease; hence, early detection is vital in ensuring the signs and symptoms of this disease are recognised to provide care for the infant. Once this has occurred, further testing is used to detect high levels of NAA in the body. For example:

• Urine test: Gas chromatography mass spectrometry is used to detect NAA levels in the urine
• Brain scan: Proton magnetic resonance spectrometry can detect high levels of NAA in the brain. MRI scans show the significant myelin loss as well as grey matter changes in the basal ganglia, showing how this causes a lack of development skills⁶
• Blood and spinal fluid: High levels of NAA are also tested in the blood and CSF
• Molecular genetic testing: This will confirm the diagnosis by identifying the ASPA gene variants that cause this disease, as two variants of this gene will confirm the diagnosis
• Enzyme activity testing in the skin cells or white blood cells can check for the enzyme aspartoacylase, as a lack of this causes an increase in NAA, as it cannot break this down

What are the types of prenatal testing that parents can use?

If both parents are carriers for the ASPA gene variant, they can undertake prenatal testing, in which there are lots of different options for:

• Chorionic Villus Sampling checks placental cells for ASPA gene variants at 10-12 weeks of pregnancy
• Amniocentesis measures the NAA levels in the amniotic fluid around the baby at 16-18 weeks of pregnancy 

Summary

Canavan disease is a neurological disorder in which the gene variant ASPA increases the levels of NAA in the brain, impacting the white matter of the brain. Hence, causing a wide range of symptoms such as poor head control, seizures but mainly a lack of motor and developmental skills like poor head control. Other symptoms are also prevalent, such as difficulties in swallowing and feeding, sleep disturbances, and reduced vision, with symptoms usually beginning at 3 to 5 months. A range of techniques and testing are used to diagnose this disease, by looking at the levels of NAA in the body, such as brain scans, as well as urine testing. Thus, it is essential to understand the signs and symptoms of Canavan disease as early as possible to enable timely referral and supportive care for both patients and parents.

FAQs

How is this disease inherited?

It is an autosomal recessive condition, so having prenatal testing is vital in determining if their baby will also be affected.

Is there a cure for this disease?

No. Treatment occurs due to the symptoms present in the individual, as well as providing support to the patient and their families. In severe forms of this disease, adequate nutrition and hydration are focused on managing infectious diseases.

What are the types of treatments which can manage symptoms?

• Physical therapy to help with posture
• Clinical courses to aid with communication skills
• Early intervention and special education programmes
• Anti-epileptic drugs to treat seizures
• Botox to aid with spasticity

What are the main symptoms of canavan disease that doctors suspect in this disease 

• Poor head control
• Macrocephaly (enlarged head)
• Delayed developmental skills

Is this disease life-threatening 

There can be complications at different stages of this disease that can become severe, though this will vary between different affected individuals. However, for most, they will live into their first two decades, with a small number surviving beyond this point.