DOCTOR'S VIEWS ARCHIVE

Canavan Disease -- Genetic Screening Advised

The Committee on Genetics of the American College of Obstetricians and Gynecologists (ACOG) has recommended that persons of Eastern and Central European (Ashkenazi) Jewish descent be offered screening for Canavan disease, a progressive fatal genetic disorder of the central nervous system. The screening would be for the detection of carriers of the gene that causes the inherited disorder. About 90% of the six million Jews in the United States are of Ashkenazu descent and are possible carriers (see below).

When a child with Canavan disease is between 3 and 6 months of age, the signs and symptoms of the disorder usually begin to appear. These include developmental delay (significant motor slowness), enlargement of the head (macrocephaly), loss of muscle tone (hypotonia), poor head control, and severe feeding problems.

In time, as the disease progresses, there are convulsions (seizures), deterioration of the nerve to the eye (optic atrophy), blindness, heartburn (gastrointestinal reflux), and difficulties swallowing.

There is currently no effective treatment for the disease and no cure in sight. Most children with Canavan disease die before the age of 10.

Canavan disease is due to the deficiency of an enzyme, aspartoacylase. This enzyme deficiency leads to increased excretion in the urine of a substance called N-acetylaspartic acid (NAA).

The diagnosis of Canavan disease can be made by finding an increased level of NAA in the urine. The abnormally high levels of NAA lead to a loss of insulation (demyelination) and spongy degeneration of the brain. An alternative name for Canavan disease is spongy degeneration of the central nervous system.

Like the more well-known Tay-Sachs disease (another progressive fatal genetic disorder of the CNS), Canavan disease is inherited as an autosomal (not linked to a sex chromosome) recessive condition. Both parents carry a single Canavan gene, which has no ill effect. However, each of their children runs a 1 in 4 risk of receiving both of their Canavan genes and, therefore, having this dread disease.

Like Tay-Sachs disease, Canavan disease is far more prevalent among individuals of European Jewish (Ashkenazi) background than the general population. About 1 in 40 persons in the Ashkenazi Jewish population is a carrier for Canavan disease. Thus, the risk of affected children in this population is about 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. Molecular testing of a blood sample for the most common Canavan disease mutations identifies about 97% of Ashkenazi Jewish carriers and 40-50% of the non-Jewish carriers.

If one parent is of Ashkenazi background or has a family history of Canavan disease, that parent should be screened. If that person is a carrier, then the other parent should also be screened.

When both parents are carriers of a Canavan disease gene, prenatal DNA diagnosis can be done by chorionic villus sampling (CVS) or amniocentesis.

Because ACOG recommendations tend to define the standard of care in obstetrics and gynecology, it seems very likely that Ashkenazi Jews in the U.S. will routinely be offered carrier screening for Canavan disease.


Last Editorial Review: 4/30/1999 5:50:00 PM