Canavan Disease

Updated October 11, 2019

This article was scientifically reviewed by YourDNA

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A list of references is also included at the bottom of this article.

What is Canavan Disease?

Canavan disease damages the ability of nerve cells in the brain to send and receive messages 1.

It is a rare inherited disorder that is one of a larger group of genetic conditions known as leukodystrophies.

What's in this Guide?

Disclaimer: Before You Read

It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.

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All leukodystrophies affect the myelin sheath, which is the material that surrounds and protects nerve cells.

When damage to the sheath takes place, it can slow down or block nerve impulse messages between the brain and the rest of the body.

The disease was first described by Myrtelle Canavan, an American neuropathologist, in a 1931 scientific paper.

Leukodystrophies appear when children are infants or in early childhood. Children may appear initially healthy, but symptoms gradually appear and get worse over time 2.

This can lead to problems with hearing, vision, speaking, and movement.

Other names for Canavan disease include:

  • ACY2 deficiency
  • aminoacylase 2 deficiency
  • Aspa deficiency
  • aspartoacylase deficiency
  • Canavan's disease
  • Spongy degeneration of the brain
  • Canavan - van Bogaert disease

Canavan disease is caused by a mutation in the gene of an enzyme called aspartoacylase (ASPA).

Aspartoacylase is also known as aspartic acid and breaks down the concentrated brain chemical known as N-acetyl-aspartate.

Researchers believe that controlling N-acetyl-L-aspartate levels is essential for developing and maintaining white matter in the brain.

Neonatal/infantile Canavan disease is the most severe form of the disorder. It is also the most common and generally appears infants starting at 3 to 5 months of age.

Infants have trouble with motor skills such as turning over, controlling head movements, or sitting up without support.

Macrocephaly (an unusually large head size), weak muscle tone, swallowing problems, seizures and sleep problems may also develop over time 3.

A juvenile form of Canavan disease is less common and affects individuals with milder symptoms.

In some cases, delays in motor and speech skills develop in childhood, but they are so minor that they are not diagnosed as being caused by Canavan disease.

Life expectancy for people with Canavan disease varies. Those with the neonatal/infantile form usually only live until childhood, although there are some exceptions of people who live into adolescence and adulthood.

According to research, people with the juvenile form do not have a shortened lifespan.

There are no cures for Canavan disease or any of the leukodystrophies. Medicines, speech therapy, and physical therapy might help with symptoms.

Causes and the Genetic Pattern of Inheritance for Canavan Disease

Canavan disease is an inherited condition that occurs when mutations of the ASPA gene pass from one generation to the next. There are more than 80 reported mutations that have been identified.

It occurs in people of all ethnic backgrounds but is most common in individuals of Ashkenazi (eastern and central European) Jewish heritage 4.

Research indicates this disorder affects 1 in 6,400 to 13,500 people in the Ashkenazi Jewish population 5.

This is because people in an ethnic group often share certain versions of their genes that are passed down from common ancestors.

If one of these shared genes contains a disease-causing mutation such as Canavan disease, a particular genetic disorder may be seen more frequently in that group.

Tay-Sachs disease is another condition more likely to occur among people of Ashkenazi Jewish or French Canadian ancestry.

Canavan disease is inherited in an autosomal recessive pattern. This means both copies of the gene in each cell have mutations.

Each parent carries one copy of the mutated gene. With an autosomal recessive condition, parents typically do not show signs or symptoms of the disease.

Canavan disease is caused by the absence of the enzyme aspartoacylase (ASPA).

ASPA breaks N-acetylaspartate acid (NAA) into building blocks essential for building a fatty membrane (white matter) that forms a proactive coating around each nerve. This ensures the nerve functions properly 6.

Who Gets Canavan Disease?

Canavan disease affects all ethnic groups, but it is more frequent in individuals with Ashkenazi Jewish descent.

The frequency of being a carrier is estimated to be as high as one out of every 40 to 60 people.

A carrier will not necessarily have signs and symptoms, but the mutated gene will be present. When both parents are carriers, each child has a 25% of having the disease 7.

Research indicates Canavan disease affects 1 in 6,400 to 13,500 people in the Ashkenazi Jewish population 8.

Of these, it is more frequent among Ashkenazi Jews from eastern Poland, Lithuania, and western Russia, and among Saudi Arabians.

In the Ashkenazi Jewish population, two mutations cause the vast majority of Canavan disease.

One of these replaces the amino acid, glutamic acid with the amino acid alanine at position 285 of the enzyme (written as Glu285Ala or E285A).

This genetic change dramatically reduces the amount of functional aspartoacylase.

The other mutation, written as Tyr231Ter or Y231X, prematurely stops protein production and leads to an abnormally small, nonfunctional version of the enzyme.

The frequency of Canavan disease among the general population is not known.

Signs and Symptoms of Canavan Disease

Signs and symptoms of neonatal Canavan disease appear early in life and include:

  • Late developmental milestones, such as head control due to poor muscle tone, especially in the neck. This includes a lack of head control when the baby moves from a lying to a sitting position
  • Abnormal posture with flexed arms and straight legs
  • Food material flows back into the nose
  • Feeding problems
  • Unusually large head size (macrocephaly)
  • Irritability
  • Poor visual tracking, or blindness
  • Reflux with vomiting
  • Seizures
  • Severe intellectual disability
  • Swallowing difficulties
  • Joint stiffness
  • Exaggerated reflexes

People suffering from the milder form of juvenile Canavan disease will have milder symptoms that are not life-threatening and may produce only minor disabilities.

Neonatal/infantile Canavan disease is the most common and most severe form of the condition.

Infants appear normal for the first few months of life, but by age 3 to 5 months, developmental problems are noticeable.

Affected infants sometimes do not develop motor skills such as turning over, controlling head movement, and sitting without support.

Other common features of this Canavan disease include weak muscle tone (hypotonia), an unusually large head size (macrocephaly), and irritability.

Other features include feeding and swallowing difficulties, seizures, and sleep disturbances.

Some children will develop more skills in these areas, depending on the severity of the disease in an individual.

The mild/juvenile form of Canavan disease is uncommon. Affected individuals have delayed speech development and motor skills starting in childhood.

These delays may be so slight they are never recognized as being caused by Canavan disease.

The life expectancy for individuals with Canavan disease varies and depends on the quality of care and what mutation or mutations the affected child is born with.

Children born with the most common severe form of the disease and can live into their teens or twenties with excellent care. Many factors determine how long a person can live with Canavan disease 9.

Diagnosis of Canavan Disease

The diagnosis of Canavan disease can be challenging. Because it is a mutation of the ASPA gene of chromosome 17, genetic testing can reveal the presence of the disease or if someone is a carrier.

The ASPA gene produces an enzyme called Aspartoacyase. Aspartoacylase is responsible for breaking down N-Acetyl Aspartic Acid, or NAA in the brain.

Children born with Canavan disease have extremely high levels of NAA. This is detected by urinalysis. But the most accurate way to test for Canavan disease is through DNA blood testing.

There are over 80 identified mutations of the ASPA gene, and due to so many variations, there is a spectrum of severity in Canavan disease.

The Genetic Testing Registry (GTR) provides information about the genetic tests for Canavan disease. GTR is a resource for health care providers and researchers.

Patients with specific questions about genetic testing should contact a health care provider or a genetics professional.

Orphanet lists international laboratories offering diagnostic testing for Canavan disease.

Healthcare professionals may also look at a patient's medical history, symptoms if there have been any family genetic testing, and laboratory results to help accurately diagnose Canavan disease.

Canavan disease also will cause abnormalities to appear in a CT in the form of low radiographic attenuation.

This will make it stand out from the unaffected part of a person's gray matter.

An MRI will confirm megalencephaly and provides more detail of the white matter disease, which is typically diffuse, bilateral.

Are There Prenatal Tests for Canavan Disease?

Pre-natal tests for Canavan disease include:

  1. DNA analysis
  2.  Blood chemistry
  3.  CSF chemistry
  4.  Genetic testing for aspartoacylase gene mutations
  5.  Head CT scan
  6.  Head MRI scan
  7.  Urine or blood chemistry for elevated aspartic acid

Carrier Screening for Canavan Disease

If both parents are carriers of the mutated gene, a child has a 25% chance of getting Canavan disease 10.

Genetic counseling and screening can determine if the mutated gene is present before parents decide to go forward with starting a family.

A genetic counselor can provide advice and information on a wide variety of genetic issues, including Canavan disease, before conception, or if a mother is already pregnant, before birth.

Carrier screening is especially important for Ashkenazi Jews because certain diseases, including Canavan disease, Tay-Sachs, Gaucher disease, and Familial Dysautonomia, occur more frequently in this population.

Treatments and Care Options for Canavan Disease

There is no specific treatment available to cure Canavan disease.

Supportive care is critical to ease the symptoms of the disease. This means supplying patients with adequate nutritional needs and hydration, protecting the airway and treating infectious diseases.

Physical therapy can also help to reduce the severity of contractures and improve motor abilities and seating posture. Seizures are treated with anti-epileptic drugs.

At times, a feeding tube may is inserted through an endoscopic procedure. After a camera is inserted through the mouth and into the stomach, a small surgical cut is made on the stomach, and a G-tube is inserted.

The hollow tube is used to deliver food and water to the patient.

Special education programs may assist with communication skills.

In addition, after analyzing information for 24 years from three separate trials, A combination of medications known as a Canavan Cocktail was developed by Dr. Paola Leone and her team at the Cell and Gene Therapy Center at Rutgers New Jersey Medical School.

Lithium and gene therapy continued to be studied but have not enjoyed breakthrough status yet.

Genetic therapies are in trials and appear to reduce the level of NAA in the brain.

In gene therapy, healthy copies of the defective ASPA gene are inserted into the brains of affected children 11.

These genes produce aspartoacylase, which is required to breakdown NAA. Children treated with gene therapy have shown significant improvement, but more research is necessary to confirm these advances.

The best medical advice and treatment is provided by doctors who have experience with Canavan disease.

Specialists are found through advocacy organizations, clinical trials, or by contacting authors of articles published in medical journals.

In broader terms, researchers are testing bone marrow transplantation as a treatment for some of the leukodystrophies.

Complications Associated with Canavan Disease

There are a number of severe complications with Canavan disease that are often fatal. Among these are:

  • Mental retardation
  • Optic atrophy and blindness
  • Hearing loss
  • Decreased motor skills that continue to diminish as the disease progresses
  • Uncontrolled rigid extensions and rotations of the arms, legs, fingers, and toes or paralysis
  • Intellectual disabilities
  • More prone to infections
  • Problems swallowing
  • Sleep disturbances
  • Seizures
  • High blood pressure
  • Nasal regurgitation
  • Nystagmus
  • Acid reflux
  • Vomiting
  • Hypotonia that can develop into spasticity

Some of these complications are treated with medicine or physical therapy.

The Prognosis of Canavan Disease

The prognosis for people with Canavan disease is poor for those with the more severe neonatal form of the disease.

Death can occur as early as 18 months and for most sufferers, usually before age 10. A few cases will survive into adolescence or their early 20s.

Part of the life expectancy depends on the clinical course of the disease and the level of medical care that the patient receives.

Some research is underway to develop a treatment for Canavan disease. Aspa Therapeutics, a subsidiary of BridgeBio Pharma, is conducting a natural history study to help advance an upcoming trial for Canavan patients.

The goal is to use a gene therapy that will deliver functional copies of the ASPA gene throughout the body and into the brain to correct the disease.

Scientists have developed animal models for Canavan disease and are using the models to test potential therapeutic strategies.

Three strategies are currently under investigation are:

  1. gene transfer to the brain in order to replace the mutated gene for the enzyme
  2. metabolic therapy to provide a crucial missing metabolite (acetate)
  3. enzyme therapy where the enzyme aspartoacylase is engineered to be able to enter the brain and is injected in the bloodstream.

Although more work needs to be done, encouraging results have been obtained using these strategies.

What to do Next: Living with Canavan Disease

There is currently no cure for Canavan disease. Various speech and motor skill therapies can help to reduce the impact of symptoms and stave off the full effects of the disease.

However, those affected with the neonatal form of Canavan disease have limited options for enjoying a good quality of life for many years.

The following resources can provide more information on Canavan disease:

National Organization for Rare Disorders

National Tay-Sachs & Allied Diseases Association

The Canavan Disease Patient Insights Network (PIN)

This is a network to understand and share the health experiences of people with Canavan Disease.

Privacy is protected using Patient Crossroads so participants can share de-identified data if they choose.

Participants can also choose to receive notice of clinical trial recruitment and the latest research news.

Canavan Foundation, Inc.

Genetic Alliance

Canavan Disease Research

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Referenced Sources

  1. Canavan disease.
    Genetics Home Reference. Reviewed: April 2015, Published: September 10, 2019.
  2. Canavan Causes.
    National Tay-Sachs and Allied Diseases. Last Updated: 13 March 2015.
  3. About Canavan Disease.
    Canavan Research Illinois. Retrieved online, September 2019.
  4. Canavan disease.
    Genetics Home Reference. Reviewed: April 2015, Published: September 10, 2019.
  5. Canavan disease.
    Genetics Home Reference. Reviewed: April 2015, Published: September 10, 2019.
  6. Canavan Causes.
    National Tay-Sachs and Allied Diseases. Last Updated: 13 March 2015.
  7. Canavan Causes.
    National Tay-Sachs and Allied Diseases. Last Updated: 13 March 2015.
  8. Canavan disease.
    Genetics Home Reference. Reviewed: April 2015, Published: September 10, 2019.
  9. About Canavan Disease.
    Canavan Research Illinois. Retrieved online, September 2019.
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    National Tay-Sachs and Allied Diseases. Last Updated: 13 March 2015.
  11. Canavan Disease.
    National Organization for Rare Disorders. Retrieved online, September 2019.