Canavan Disease

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What is Canavan disease?

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 are characterized by degeneration of myelin, which is the fatty covering that insulates nerve fibers.

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 3 to 5 months of age, affected infants begin having problems with development including a delay in motor skills such as turning over and sitting. These infants typically also have weak muscle tone (hypotonia), increased head size (macrocephaly), abnormal posture, and mental retardation. Feeding and swallowing difficulties, seizures, and sleep disturbances may also develop.

How common is Canavan disease?

This disorder occurs in 1 in 6,400 to 13,500 people of Ashkenazi (eastern and central European) Jewish heritage. Although it is more common in this population, the condition is seen in people of all ethnic backgrounds. The incidence in other populations is unknown.

What genes are related to Canavan disease?

Mutations in the ASPA gene cause Canavan disease.

The ASPA gene makes 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. Mutations in the ASPA gene prevent the breakdown of NAA, allowing this substance to accumulate to toxic levels in these cells. A buildup of NAA leads to the destruction of myelin, the covering that normally insulates and protects nerve cells. As a result, the exposed nerve fibers deteriorate, causing the serious signs and symptoms of Canavan disease.

How do people inherit Canavan disease?

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.

Source: National Institutes of Health

Research on central nervous system disease cell biology described by scientists at Uniformed Services University of the Health Sciences

"During early postnatal central nervous system (CNS) development, the expression of lipogenic enzymes in oligodendrocytes, including the NAA-degrading enzyme aspartoacylase (ASPA), is increased along with increased NAA production in neurons. NAA is transported from neurons to the cytoplasm of oligodendrocytes, where ASPA cleaves the acetate moiety for use in fatty acid and steroid synthesis. The fatty acids and steroids produced then go on to be used as building blocks for myelin lipid synthesis. Mutations in the gene for ASPA result in the fatal leukodystrophy Canavan disease, for which there is currently no effective treatment. Once postnatal myelination is completed, NAA may continue to be involved in myelin lipid turnover in adults, but it also appears to adopt other roles, including a bioenergetic role in neuronal mitochondria. NAA and ATP metabolism appear to be linked indirectly, whereby acetylation of aspartate may facilitate its removal from neuronal mitochondria, thus favoring conversion of glutamate to alpha ketoglutarate which can enter the tricarboxylic acid cycle for energy production. In its role as a mechanism for enhancing mitochondrial energy production from glutamate, NAA is in a key position to act as a magnetic resonance spectroscopy marker for neuronal health, viability and number. Evidence suggests that NAA is a direct precursor for the enzymatic synthesis of the neuron specific dipeptide N-acetylaspartylglutamate, the most concentrated neuropeptide in the human brain. Other proposed roles for NAA include neuronal osmoregulation and axon-glial signaling. We propose that NAA may also be involved in brain nitrogen balance," wrote J.R. Moffett and colleagues, Uniformed Services University of the Health Sciences.

The researchers concluded: "Further research will be required to more fully understand the biochemical functions served by NAA in CNS development and activity, and additional functions are likely to be discovered."

Moffett and colleagues published their study in Progress In Neurobiology (N-Acetylaspartate in the CNS: from neurodiagnostics to neurobiology. Progress In Neurobiology, 2007;81(2):89-131).

For additional information, contact J.R. Moffett, Uniformed Services University of the Health Sciences, Dept. of Anatomy, Physiology and Genetics, Building C, 4301 Jones Bridge Rd., Bethesda, MD 20814 USA.

The publisher of the journal Progress In Neurobiology can be contacted at: Pergamon-Elsevier Science Ltd., the Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, England.

Keywords: United States, Bethesda, Central Nervous System Disease Cell Biology, Cell Biology, Central Nervous System Disease, Central Nervous System Infection, Neurobiology.

This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2007, Pain & Central Nervous System Week via NewsRx.com.