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Canavan Disease
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Types and clinical signs
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This is a severe degenerative disease of the brain that is caused by the accumulation
of an abnormal substance called acetylaspartic acid. The disease begins to manifest
2 - 4 months after birth, and the first signs are muscle flaccidity and convulsions.
Severe motor and mental retardation develop, and most patients
die by the age of three years.
Nowadays there is a trial treatment, still at the research stage, which is being
carried out abroad. This involves injecting the missing enzyme, aspartoacylase,
into the bloodstream, from where it is transported to the cells. The results are
not yet complete, but it appears that the treatment does provide some benefit in
all parameters, and arrests the development of the disease to a degree that has
yet to be determined. It may be more effective if given before the onset of the
signs and complications of the disease.
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Inheritance pattern
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Autosomal
recessive.
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Penetrance
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Full
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Associated features that can be demonstrated in tests performed during pregnancy
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There are no specific ultrasound signs or associated defects.
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What is the risk of recurrence in a subsequent pregnancy?
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For a couple who has already had an affected child, the risk is 25% in every subsequent
pregnancy.
This also applies to a couple where both partners have been found to carry mutations
for Canavan disease.
When only one parent carries the abnormal gene, there is no risk that any of their
offspring will have the disease;
however, in such families there is a 50% chance that the infant will be a carrier,
but he himself will be healthy, like the carrier parent.
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The risk for more distant relatives depends on the degree of relationship between
the relatives and the affected individuals, the ethnic groups of their partners,
the presence of family members with Canavan disease in the partner's families, consanguinity between the
parents, if present, etc. The risk is established within genetic counseling.
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Molecular genetic information
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The gene for the disease
The gene for aspartoacylase
Location
The short arm of chromosome 17.
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Genetic testing
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Diagnostic testing
A direct test can be performed to identify the mutation in the gene by testing for
the common mutations. See:
Testing the disease-causing gene for mutations that are common in a specific ethnic
group - autosomal recessive diseases.
Carrier testing
Among Jews, most of the affected children have been found to be Ashkenazim. Mutations
in the gene have also been found in non-Jews and non-Ashkenazi Jews, but they are
rare in these groups. The carrier frequency in the healthy Ashkenazi Jewish population
is between 1:40 and 1:60. There are two main mutations known today that cause this
disease in Ashkenazi Jews. Between them these are responsible for about 98% of the
cases of Canavan disease in Israel. In Jews of other ethnic groups, carriers cannot
be identified. It is therefore advisable to perform tests in couples when one of
the partners is of full or partial Ashkenazi origin.
Carrier status testing in relatives of patients with Canavan disease
It is important that relatives of patients with Canavan disease clarify which mutations
are present in the patient or parents in their family in order to ascertain that
they are included in the battery of mutations routinely tested for - otherwise it
will be necessary to expand the list of mutations tested for and/or examine the
partner. This will be discussed in genetic counseling. See also:
Introduction to cystic fibrosis, Gaucher disease, Canavan disease, familial dysautonomia,
Bloom syndrome and Fanconi anemia.
Fetal testing
Same as the diagnostic test.
Prenatal diagnosis (amniocentesis)
can also be offered to each couple who has had an affected child. The best way is
after identifying the mutations in the parents, but if these are not found, indirect
linkage analysis can be performed. See: Indirect testing for genetic
markers in a family that has one or more patients - when there is only one gene
that can cause the disease - autosomal recessive diseases.
Preimplantation diagnosis (before the embryonic cells implant in the uterine wall)
can also be offered for this disease - this is performed in special centers, mainly
overseas, and in special cases this can be considered within genetic counseling.
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