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Canavan disease

Canavan-van Bogaert-Bertrand disease, Spongy degeneration of the central nervous system, Von Bogaert-Bertrand disease, Aspartoacylase deficiency, ASPA deficiency, ASP deficiency, ACY2 deficiency, Aminoacylase 2 deficiency

Overview

Canavan disease is an inherited disorder that causes progressive damage to nerve cells in the brain. This disease is one of a group of genetic disorders called leukodystrophies. Leukodystrophies disrupt the growth or maintenance of the myelin sheath, which is the fatty covering that insulates nerve fibers. Canavan disease is caused by mutations in the ASPA gene and is inherited in an autosomal recessive pattern. While it occurs in people of all ethnic backgrounds, it is most common in people of Ashkenazi (eastern and central European) Jewish heritage, and among Saudi Arabians.

Symptoms - Canavan disease

The signs and symptoms of this disease usually begin in early infancy; however, the course of the condition can be quite variable. Infants with Canavan disease typically appear normal for the first few months of life. By age 3 to 5 months, affected infants begin having problems with development, including a delay in motor skills such as turning over, controlling head movement, and sitting without support. These infants typically also have weak muscle tone (hypotonia), unusually large head size (macrocephaly), abnormal posture, and intellectual disability. Feeding and swallowing difficulties, seizures, and sleep disturbances may also develop.

The life expectancy for people with Canavan disease varies. Most affected individuals live only into childhood, although some survive into adolescence or beyond.

Causes - Canavan disease

Mutations in the ASPA gene cause Canavan disease. The ASPA gene provides instructions for making an enzyme called aspartoacylase. This enzyme normally breaks down a compound called N-acetyl-L-aspartic acid (NAA), which is predominantly found in nerve cells in the brain. Although the precise function of NAA is unclear, it probably plays a role in the production of myelin.

Mutations in the ASPA gene prevent the normal breakdown of NAA. Recent studies suggest that if NAA is not broken down properly, the resulting chemical imbalance may interfere with the formation of myelin as the nervous system develops. A buildup of NAA also leads to the progressive destruction of existing myelin around nerve cells. Nerve fibers without this protective covering malfunction and die, damaging the brain and causing the serious signs and symptoms of Canavan disease.

Canavan disease is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. When both parents are found to carry the Canavan gene mutation, there is a one in four (25%) chance with each pregnancy that the resulting child will be affected with Canavan disease.

Prevention - Canavan disease

Genetic counseling is recommended for prospective parents with a family history of Canavan disease, and should be considered if both parents are of Ashkenazi Jewish descent. For this group, DNA testing can almost always tell if one or both parents is a carrier.

Diagnosis - Canavan disease

Healthcare professionals typically look at a person's medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis.

Prognosis - Canavan disease

The prognosis for Canavan disease is poor. Death usually occurs before age 4, although some children may survive into their teens and twenties. Life expectancy is variable. Some children die in the first few years of life while others may survive into their teens and twenties. Prognosis often depends upon the clinical course of the disease as well as the level of medical care provided.

Treatment - Canavan disease

Canavan disease causes progressive brain atrophy. There is no cure, nor is there a standard course of treatment. Treatment is symptomatic and supportive. Management may include provision of adequate nutrition and hydration, treatment of infectious diseases, and protection of the airway. Physical therapy may help to minimize contractures and maximize motor abilities and seating posture. Special education programs can enhance communication skills. Seizures are treated with anti-epileptic drugs. Gastrostomy can help to maintain adequate food intake and hydration when swallowing difficulties exist.

Resources - Canavan disease

  • NIH
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