Van Bogaert-Bertrand syndrome

Related Terms

ASP deficiency, ASPA deficiency, aspartoacylase, aspartoacylase deficiency, Canavan's leukodystrophy, Canavan-Van Bogaert-Bertrand disease, CD, myelin, myelin sheath, spongy degeneration of the brain, spongy degeneration of the central nervous system, spongy degeneration of the neuroaxis, Van Bogaert-Bertrand syndrome.

Background

Canavan disease is a rare and fatal inherited disease that leads to the progressive degeneration of the brain and nervous system. Symptoms, which appear shortly after birth and worsen rapidly, typically include intellectual disabilities (formerly called mental retardation), loss of previously acquired muscle coordination, abnormal muscle tone, an abnormally large head, and poorly controlled head movement. Hearing loss, blindness, and paralysis may also occur.
Canavan disease is one of many disorders that are called leukodystrophies. These disorders are characterized by abnormal growth or development of the myelin sheath, the fatty substance that protects and insulates the nerve fibers in the brain and spinal cord. Myelin is made up of at least 10 different chemicals. Each of the leukodystrophies affects one of these substances.
Canavan disease may affect anyone, regardless of their race, ethnicity, or gender. However, it is most common among Ashkenazi Jewish individuals from eastern Poland, Lithuania, and western Russia. It is also common among Saudi Arabians. It is estimated to affect one out of 6,400-13,500 people of Ashkenazi Jewish heritage. The incidence is unknown in other populations.
There is currently no cure or specific treatment for Canavan disease. Instead, therapy focuses on reducing the severity of symptoms and making the patient as comfortable as possible. The condition ultimately leads to death, usually during infancy. Most patients die before they reach 18 months of age. However, some may live to be teenagers and even fewer live until they reach their 20s. Patients with Canavan disease require around-the-clock care and support.

Signs and symptoms

Symptoms appear shortly after birth and worsen rapidly. Patients with Canavan disease require around-the-clock care. Common symptoms include decreased muscle tone (especially in the neck muscles, which often leads to uncontrolled head movements), abnormal posture with flexed arms and straight legs, difficulty feeding and swallowing (which may include backflow of food material into the nose), reflux with vomiting, increased head size, failure to meet developmental milestones, and intellectual disabilities (mental retardation). Towards the end-stages of the disease, patients may experience blindness, hearing loss, seizures, and paralysis.

Diagnosis

General: If Canavan's disease is suspected, a doctor may take samples of the patient's blood, urine, and/or cerebrospinal fluid (CSF). These samples are then analyzed for N-acetylaspartate acid (NAA). If high levels of NAA are detected, Canavan's disease is highly suspected and a DNA test may be performed to confirm the diagnosis.
DNA test: A DNA test is usually performed to confirm a diagnosis. A sample of the patient's blood is taken and analyzed in a laboratory for the presence of a mutated aspartoacylase gene. If a mutation is present, a positive diagnosis is made.
If a person has a family history of Canavan disease, a DNA test may be performed to determine if he/she carries a copy of the mutated aspartoacylase gene. Although a carrier does not have Canavan disease, he/she may pass a copy of the mutated gene to his/her children.
Prenatal DNA testing: If both parents are carriers of the mutated aspartoacylase gene, prenatal testing may be performed to determine if the fetus has the disorder. However, there are serious risks associated with prenatal tests. Patients should discuss the potential health benefits and risks associated with these procedures before making any medical decisions.
During amniocentesis, a long, thin needle is inserted through the abdominal wall into the uterus and a small amount of amniotic fluid is removed from the sac surrounding the fetus. The fluid is then analyzed for a mutated aspartoacylase gene. This test is performed after 15 weeks of pregnancy. Some experts estimate that the risk of miscarriage ranges from one out of 200-400 patients; it is highest when the procedure is done early in pregnancy, before the two layers of fetal membranes have sealed. A woman's particular risk depends in large part on the skill and experience of the doctor performing the procedure. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.
During chorionic villus sampling (CVS), a small piece of tissue (chorionic villi) is removed from the placenta during early pregnancy. Depending on where the placenta is located, CVS can be performed through the cervix or through the abdomen. The tissue sample is then analyzed for a mutated aspartoacylase gene. This procedure may be performed between the ninth and 14th week of pregnancy. The risks of infection or fetal damage are slightly higher than the risks of amniocentesis. Miscarriage occurs in about two out of 100 women who undergo this procedure. There appears to be an even higher risk of miscarriage with the transcervical CVS technique compared to the transabominal technique. Other factors that further increase the risk of CVS include having the procedure performed three or more times and having a fetus that is smaller than normal. The physician's skill and experience also play an important role.
Genetic counseling: Before and after genetic testing, it is recommended that people meet with genetic counselors. These professionals can help patients understand the risks of having a child with Canavan disease. A genetic counselor can also explain the different types of genetic tests, including their potential risks and benefits. These counselors can also help patients understand and interpret their test results.

Treatment

There is currently no cure or specific treatment for Canavan disease. Instead, treatment focuses on reducing symptoms. The disorder ultimately results in death, usually before the age of 18 months. Some may live until their teenage years, and even fewer may live until they reach their 20s.
Medications, called anticonvulsants, may help reduce the frequency and severity of seizures. Commonly prescribed anticonvulsants include tomipramate (Topamax?), levetiracetam (Keppra?), zonisamide (Zonegram?), phenytoin (Dilantin?), carbamazepine (Tegretol? or Carbatrol?), phenobarbital, and valproic acid (Depakene?, Depakote?).

Integrative therapies

Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of Canavan disease.

Prevention

There is currently no known way to prevent Canavan disease.
If a person has a family history of Canavan disease, genetic testing may be performed to determine if he/she carries the mutated gene. Although carriers do not have the disease, they can pass a copy of their mutated gene onto each of their children.
Prenatal DNA testing may be performed if there is a family history of Canavan disease. However, there are health risks associated with prenatal testing, including miscarriage. Therefore, patients should discuss the potential health risks and benefits before making any health-related decisions.
Before and after genetic testing, it is recommended that people meet with genetic counselors. These professionals can help patients understand the risks of having a child with Canavan disease. A genetic counselor can also explain the different types of genetic tests, including their potential risks and benefits. These counselors can help patients understand and interpret their test results.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

American Academy of Pediatrics (AAP). .
Bitto E, Bingman CA, Wesenberg GE, et al. Structure of aspartoacylase, the brain enzyme impaired in Canavan disease. Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):456-61. Epub 2006 Dec 28.
Feigenbaum A, Moore R, Clarke J, et al. Canavan disease: carrier-frequency determination in the Ashkenazi Jewish population and development of a novel molecular diagnostic assay. Am J Med Genet A. 2004 Jan 15;124(2):142-7.
Harting I, Seitz A. Canavan disease. Rofo. 2001 Oct;173(10):M275-6.
Kumar S, Mattan NS, de Vellis J. Canavan disease: a white matter disorder. Ment Retard Dev Disabil Res Rev. 2006;12(2):157-65.
National Human Genome Research Institute (NHGRI). .
National Institutes of Health (NIH). .
National Institutes of Neurological Disorders and Stroke (NINDS). .
Natural Standard: The Authority on Integrative Medicine. .

Causes

General: Canavan disease occurs when a person is born with a mutated, or abnormal, aspartoacylase gene. Normally, this gene provides the body with instructions on how to make an enzyme called aspartoacylase. This enzyme is needed to break down N-acetylaspartate acid (NAA) into aspartic acid. This process appears to be essential in order for the body to maintain myelin, a substance that protects and insulates the nerves in the brain and spinal cord.
Patients with Canavan disease are unable to produce enough aspartoacylase. As a result, NAA builds up to dangerous levels in the body, causing destruction of the myelin sheath. As a result, the exposed nerve fibers die and brain function deteriorates over time.
Inheritance: Canavan disease is considered an inherited disorder that is passed down among family members. Each gene has two variations, called alleles. One allele is inherited from each parent. Canavan disease is inherited as an autosomal recessive disorder. This means that two mutated alleles (one from each parent) of a single gene must be inherited in order for a person to develop the disorder.
A person who has only one mutated allele does not experience symptoms and is called a carrier. If one parent is a carrier, there is a 50% chance with each birth that the child will also be a carrier, and a 0% chance that the child will inherit the disease. If both parents are carriers, there is a 25% chance with each birth that the child will inherit the disease, and a 50% chance that each child will be a carrier.