Definition of Canavan disease
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Our Canavan disease Main Article provides a comprehensive look at
the who, what, when and how of Canavan disease
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Canavan disease definition - medical term A severe progressive inherited (genetic) disorder of
the central nervous system (CNS).
The signs of Canavan disease usually appear when the children are between 3 and
6 months of age. They include developmental delay (significant motor slowness),
enlargement of the head (macrocephaly), loss of muscle tone (hypotonia), poor head
control, and severe feeding problems. As the disease progresses, convulsions (seizures),
shrinkage of the nerve to the eye (optic atrophy) and often blondness, heartburn
(gastrointestinal reflux) and deterioration of swallowing develop.
Most children with Canavan disease die in the first decade of life. There is
currently no cure or effective treatment for Canavan disease.
Canavan disease is caused by a deficiency of the enzyme aspartoacylase. This
leads to increased excretion of a substance (its substrate) called N-acetylaspartic
acid (NAA) in the urine. The diagnosis of Canavan disease is made by finding an
increased level of urinary NAA (by organic acid analysis).
The abnormally high levels of NAA lead to loss of insulation (demyelination)
and spongy degeneration of the brain, which cause the ominous signs and symptoms
of Canavan disease.
As in Tay-Sachs disease (another severe progressive genetic disorder of the CNS),
Canavan disease is inherited as an autosomal recessive condition with both parents
silently carrying a single Canavan gene and each of their children running a 1 in
4 risk of receiving both of their Canavan genes and, therefore, having this dread
disease.
As in Tay-Sachs disease, Canavan disease is more prevalent among individuals
of Eastern European Jewish (Ashkenazi) background. It is estimated that the carrier
frequency in the Ashkenazi Jewish population is approximately 1 per 40. Thus, the
risk from an affected offspring in this population approximates 1 in 6,400 births.
Unlike Tay-Sachs disease, however, there do not appear to be any other high-risk
ethnic populations, although Canavan disease has been reported occasionally in individuals
of non-Ashkenazi Jewish background.
Molecular genetic (DNA) studies have revealed two specific mutations (changes)
in the gene for aspartoacylase on chromosome 17. These two mutations account for
approximately 97% of the mutations causing Canavan disease in the Ashkenazi Jewish
population. (One is a mutation in codon 285 of the aspartoacylase gene, and the
other is a mutation in codon 231.)
Genetic screening of Ashkenazi Jewish individuals for Canavan disease carriers
can be done by checking for these two mutations. Screening for Canavan disease carriers
requires molecular diagnostic methods. 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. Testing for the
most common Canavan disease mutations -- there are actually three of them -- will
identify about 97% of Ashkenazi Jewish carriers (and 40-50% of the non-Jewish carriers).
When both parents are carriers of Canavan disease mutations, prenatal diagnosis
by chorionic villus sampling (CVS) or amniocentesis can be done by DNA testing.
(In couples where one or both members have unknown mutations, biochemical analysis
of NAA levels in the amniotic fluid can be used reliably. Elevated NAA levels can
be used to detect an affected fetus.)
The Committee on Genetics of the American College of Obstetricians and Gynecologists
(ACOG) has recommended that Ashkenazi Jews be offered screening to determine if
they are carriers of Canavan disease. 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).
Common Misspellings: canavan diease, canavan desease
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