Tay-Sachs Disease

 

BACKGROUND:

Tay-Sachs Disease (TSD) is a fatal genetic disorder in children that causes the progressive deterioration of the central nervous system. It is caused by absence of the alpha subunit of hexosaminidase A (Hex A Gene). Without Hex-A, lipid called GM2 builds up abnormally in brain cells. Clinical phenotype of TSD (GM2 gangliosidosis) varies widely, ranging from:

  • Classic Tay-Sachs Disease and Sandhoff Disease:

    Infantile onset, rapidly progressive neurodegenerative disease that culminate in death before age 5.

  • Subacute GM2 Gangliosidosis:

    Onset between age 2 to 10 years, progressive psychomotor retardation, seizures and spasticity.

  • Chronic GM2 Gangliosidosis:

    Adult onset, spinocerebellar and lower motor neuron dysfunction.

INCIDENCE:

Tay-Sachs disease often occurs more frequently, though not exclusively, in a defined population of Eastern European (Ashkenazi) Jewish descent. Approximately 1 in every 25 Americans of Ashkenazi Jewish ancestry is a carrier of the TSD gene. Approximately 85% of the children affected with TSD are of Jewish ancestry although with pre-pregnancy screening, more infants born with Tay Sachs disease in the U.S. today are of non-Jewish ancestry. Tay-Sachs can occur in Jews of Sephardic origin, non-Jewish communities, Italian, and French Canadian populations.

INDICATIONS FOR TESTING:

  • Any individual of Eastern European Jewish ancestry who wants to know their carrier status.

  • Infants with progressive neurodegenerative and muscular disease.

  • Children with ataxia, slurred speech and progressive psychomotor retardation.

  • Adults with spinocerebellar and lower motor neuron dysfunction.

PROCEDURE:

A simple blood enzyme test can determine a person's Hex-A level. Total hexosaminidase activity is determined using a synthetic substrate 4-methylumbelliferyl-acetamino 2 deoxy-beta-D-glucophyranoside. Hex-A activity is determined by differential thermostability. Individuals with Tay-Sachs have a total absence of Hex-A in their blood. Generally, the carrier status can be determined by simply testing serum. However, testing of the serum in a pregnant woman is not accurate, so white cells must be used to confirm carrier status.

SAMPLE REQUIREMENTS:

  • For men who do not have a pregnant partner and non-pregnant women where birth-control pills have not been used: 10 cc of blood in a serum tube (red top).

  • For non-pregnant women with a history of Tay-Sachs in their families, or where birth control pills have been used, and for men whose wives are pregnant: 10 cc of blood in a serum tube and two lavender top tubes, each with 10 cc of blood.

  • For pregnant women, two lavender top tubes, each with 10 cc of blood.

INTERPRETATION:

It is generally accepted that persons with a Hex-A value (serum or white cell testing) above 60% of the total (hexosaminidase) level are normal. An individual with a value less than 60% but greater than 55% is inconclusive and may require DNA testing (see Molecular section). However, a value less than 50% is in the carrier range.

COUNSELING ISSUES:

Genetic counseling is a vital part of the program. Screening of the target population, particularly those of reproductive age, is advisable.

SPECIAL NOTE:

Analysis for this disorder can be accomplished by both biochemical and molecular methods (see molecular section). The use of these different technologies in complementary. The decision as to which tests are appropriate for any sample is made on a case by case basis. For further information on handling of any sample, please contact the Center.

 

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