Invitae Tay-Sachs Disease Test


Test description

The Invitae Tay-Sachs Disease test analyzes HEXA, the gene known to be associated with Tay-Sachs disease (TSD). Tay-Sachs disease is a progressive pediatric neurodegenerative disorder with symptoms ranging from classic TSD (acute infantile) to subacute juvenile and adult-onset forms that progress more slowly. It is caused by the build-up of gangliosides in the brain.

A genetic diagnosis of TSD can identify the specific subtype of the disease, guide medical management, and help predict disease progression and outcome for the patient. It can also facilitate a swift uptake of treatment.

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Primary panel (1 gene)


Add-on Sandhoff disease gene (1 gene)

Given the significant clinical overlap between Sandhoff disease and Tay Sachs disease, analyzing HEXB, the gene associated with Sandhoff, may be appropriate. The HEXB gene can be included at no additional charge.


Tay-Sachs disease (TSD)

Clinical subtypes:

  • Acute infantile (classic Tay-Sachs disease) — characterized by rapid progression and death, frequently by age 4
  • Subacute juvenile form — characterized by later onset and survival into late childhood or adolescence
  • Adult onset form — characterized by longer survival and greater variability in neurologic findings

Tay-Sachs disease (TSD) is a progressive pediatric neurodegenerative disorder that results from the toxic accumulation of GM2 ganglioside in the central nervous system. TSD is a type of hexosaminidase A deficiency—a condition caused by pathogenic variants in the gene that encodes beta-hexosaminidase A, an enzyme that is essential for breaking down GM2 ganglioside. Infants with TSD typically first present around 3-6 months with symptoms that include progressive muscle weakness, difficulty coordinating muscle movement, decreased attentiveness, and an increased startle response. Symptoms then progress to seizures, blindness, muscle stiffness, and death, usually before age 4.

Acute infantile TSD is the commonest and most severe form of hexosaminidase A deficiency. There are two additional forms, subacute juvenile and adult-onset, which have later ages of onset, more-variable neurologic findings, and less-severe disease progressions. The level of HEXA enzyme activity is inversely correlated with the severity of the disease form.

Approximately 99% of individuals with Tay-Sachs disease have two identifiable pathogenic variants in the HEXA gene.

TSD is inherited in an autosomal recessive pattern.

TSD is considered fully penetrant. The age of onset and the severity of the disorder are dependent on the specific variants in the HEXA gene and the subsequent amount of functional HEXA protein made.

Prevalence of TSD is specific to sub-population. Among the Ashkenazi Jewish, French Canadian, Pennsylvania Amish, and Louisiana Cajun population, the carrier frequency is 1 in 27 people. This corresponds to a disease frequency of approximately 1 in 3,600 in these populations. In the Irish American population, the carrier frequency is 1 in 50. In the general population, excluding these sub-populations, the carrier frequency is approximately 1 in 250, corresponding to a disease incidence of approximately 1 in 320,000 individuals.

Genetic testing can be a useful tool to decipher the cause of reduced HEXA enzymatic activity. Reduced enzymatic activity can be due to a pseudodeficiency allele or a disease-causing variant in the HEXA gene. Approximately 35% of non-Jewish individuals identified as carriers through enzyme analysis are actually pseudodeficiency carriers and not carriers of Tay-Sachs disease.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
HEXA NM_000520.4
HEXB NM_000521.3