Canavan disease: Encyclopedia of Genetic Disorders(Site not responding. Last check: 2007-10-25)
Canavan disease, which is also called aspartoacylase deficiency, spongy degeneration of the brain, and infantile spongy degeneration, results from a deficiency of the enzyme aspartoacylase.
A person with Canavan disease has changes (mutations) in both of the genes responsible for producing the enzyme aspartoacylase and has inherited one changed gene from his or her mother and one changed gene from his or her father.
Each child born to parents who are both carriers for Canavan disease has a 25% chance of having Canavan disease, a 50% chance of being a carrier and a 25% chance of being neither a carrier nor affected with Canavan disease.
Aspartoacylase activity in control cultured human fibroblasts was 9.2 +/- 1.8 nmol/h per mg protein, compared with 1.1 +/- 0.2 in seven Canavan patients and 3.5 +/- 0.9 in four patients' parents.
Canavan disease, or spongy degeneration of the brain, is a severe leukodystrophy caused by the deficiency of aspartoacylase (ASPA).
Canavan disease is an autosomal recessive leukodystrophy caused by the deficiency of aspartoacylase (ASPA).
Aspartoacylase deficiency: A rare neurodegenerative condition of infancy or childhood characterized by white matter vacuolization and demeylination that gives rise to a spongy appearance.
Aspartoacylase deficiency leads to an accumulation of N-acetylaspartate in astrocytes.
Aspartoacylase deficiency is listed as a "rare disease" by the Office of Rare Diseases (ORD) of the National Institutes of Health (NIH).
Developmental increase of aspartoacylase in oligodendrocytes parallels CNS myelination.
Canavan disease, an autosomal-recessive neurogenetic disorder, is caused by mutations in aspartoacylase, an enzyme that deacetylates N-acetylaspartate to generate free acetate in the brain.
Earlier studies have shown that aspartoacylase is primarily restricted to myelin synthesizing cells (oligodendroglia) in the CNS.
Phenotypic characterisation of the tremor mutant and AAV mediated aspartoacylase gene transfer in the rat model of ...(Site not responding. Last check: 2007-10-25)
The deletion of aspartoacylase results in a total loss of the capacity to metabolize N-acetyl-aspartate to acetate and aspartate in brain, leading to elevations in brain N-acetyl-aspartate levels, changes in cell and tissue morphology, and physical and behavioural deficits including mild akinesia and loss of normal motor coordination and balance.
Gene transfer was undertaken in tremor rat mutants, and analysis was made of gene expression and function as well as the effect of aspartoacylase expression on improving the phenotypic deficits observed in mutant animals.
Improvement was noted in the rotorod phenotype with mutant animals receiving aspartoacylase gene transfer performing better at tests of balance and coordinated locomotion than animals receiving a control vector.
The spectrum of mutations of the aspartoacylase gene in Canavan disease in non-Jewish patients.
Canavan disease is an infantile neurodegenerative disease that is caused by mutations in the gene encoding the enzyme aspartoacylase.
This study demonstrates that within white matter, aspartoacylase is an integral component of the myelin sheath where it is ideally situated to produce acetyl groups for synthesis of myelin lipids.
Summary: Canavan's disease (Canavan-van Bogaert-Bertrand disease) or spongy degeneration of the brain is an autosomal recessive leukodystrophy due to abnormal aspartoacylase.
Diagnostic Test: quantitation of acetylaspartic acid in urine and aspartoacylase level (accumulation of abnormally high level of non-functional enzyme) in cultured fibroblasts.
Aspartoacylase is not present in plasma or blood cells.
Genetic testing for aspartoacylase gene mutations: Since the genetic basis of the disease is known to be a defect in the gene encoding aspartoacylase, the DNA of the child can be tested to look for mutations in this gene.
It is caused by a deficiency in the gene encoding a protein called aspartoacylase.
Aspartoacylase in needed to break down N-acetyl-L-aspartate (NAA), a molecule that is thought to be involved in the removal of water from certain types of brain cells, as well as in the formation of myelin lipids.
Canavan Disease(Site not responding. Last check: 2007-10-25)
The rare disorder is caused by defective aspartoacylase enzyme.
In the case of Canavan disease, a defect in the enzyme aspartoacylase is responsible for the destruction of the myelin.
Unless the aspartoacylase gene inherited from the mother and the gene inherited from the father are both defective, their child will not have Canavan disease (i.e.
The NTSAD Diseases Family: Canavan Disease(Site not responding. Last check: 2007-10-25)
In CD the white matter deteriorates because affected children have a deficiency of the enzyme aspartoacylase, which leads to the accumulation of a chemical, called N-acetyl-aspartic acid (NAA), in the brain.
A parent who is a carrier is healthy because he or she has one functional copy of the gene which produces a sufficient amount of the enzyme.
Biochemical tests for aspartoacylase activity are not sensitive enough to detect carriers, but DNA testing of Ashkenazi Jewish couples can tell with over 95% certainty whether either or both parents is a carrier.
Specifically, this mutation replaces the amino acid glutamic acid with the amino acid alanine at position 285 of the enzyme (written as Glu285Ala or E285A).
This mutation substitutes the amino acid glutamic acid for the amino acid alanine at position 305 of aspartoacylase (written as Ala305Glu or A305E).
Mutations in the ASPA gene lead to reduced or absent activity of aspartoacylase.
Kaul R. Gao G.P. Balamurugan K. Matalon R. "Cloning of the human aspartoacylase cDNA and a common missense mutation in Canavan disease.";
Shaag A. Anikster Y. Christensen E. Glustein J.Z. Fois A. Michelakakis H. Nigro F. Pronicka E. Ribes A. Zabot M.-T. Elpeleg O.N. "The molecular basis of canavan (aspartoacylase deficiency) disease in European non-Jewish patients.";
Sistermans E.A. de Coo R.F. van Beerendonk H.M. Poll-The B.T. Kleijer W.J. van Oost B.A. "Mutation detection in the aspartoacylase gene in 17 patients with Canavan disease: four new mutations in the non-Jewish population.";
Canavan disease is due to the deficiency of an enzyme, aspartoacylase.
Molecular genetic (DNA) studies have revealed two specific mutations (changes) in the gene for aspartoacylase on chromosome 17.
Simple enzyme tests, as commonly used in Tay-Sachs screening, cannot be used for Canavan disease because the activity of the deficient enzyme, aspartoacylase, is not detectable in blood.
Aspartoacylase deficiency does not affect N-acetylaspartylglutamate level or glutamate carboxypeptidase II activity in the knockout mouse brain.
Aspartoacylase (ASPA)-deficient patients [Canavan disease (CD)] reportedly have increased urinary excretion of N-acetylaspartylglutamate (NAAG), a neuropeptide abundant in the brain.
Whether elevated excretion of urinary NAAG is due to ASPA deficiency, resulting in an abnormal level of brain NAAG, is examined using ASPA-deficient mouse brain.
Canavan disease is caused by a deficiency of the enzyme aspartoacylase.
Because ACOG recommendations tend to set the standards of practice in obstetrics and gynecology, it seems highly likely that Ashkenazi Jews in the U.S. will be routinely offered carrier screening for Canavan disease in regard to pregnancy planning.
Alternative names for Canavan disease include spongy degeneration of the central nervous system, Canavan-Van Bogaert-Bertrand disease, and several names of a biochemical nature (aspartoacylase deficiency, ASPA deficiency, ASP deficiency, aminoacylase 2 deficiency, and ACY2 deficiency).
Janson CG, Kolodny EH, Zeng BJ, Raghavan S, Pastores G, Torres P, Assadi M, McPhee S, Goldfarb O, Saslow B, Freese A, Wang DJ, Bilaniuk L, Shera D, Leone P. Mild-onset presentation of Canavan's disease associated with novel G212A point mutation in aspartoacylase gene.
Characterization of human aspartoacylase: the brain enzyme responsible for Canavan disease.
Identification and characterization of novel mutations of the aspartoacylase gene in non-Jewish patients with Canavan disease.
