Invitae Sandhoff Disease Test


Test description

The Invitae Sandhoff Disease Test analyzes the hexosaminidase B (HEXB) gene. Pathogenic variants in HEXB are known to cause Sandhoff disease. Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives.

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Primary panel (1 gene)


Add-on Tay-Sachs disease gene (1 gene)

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


Sandhoff disease

Sandhoff disease is a rare progressive neurodegenerative lysosomal disorder in which lipid-containing cells accumulate, affecting the body and central nervous system. It is clinically indistinguishable from Tay Sachs disease. The infantile form is the most severe and most common, with onset typically between three and six months of age. Infants develop seizures and lose developmental milestones, vision, and hearing. A characteristic cherry-red spot is seen on ophthalmologic examination. Organomegaly may be observed. The infantile form of this disorder is fatal, with death usually before four years of age.

Juvenile and adult onset cases of Sandhoff are less common, more mild in presentation, and more slowly progressive. Presentation in older individuals may include ataxia, cognitive impairment, and mental illness; cherry-red spots may not be present. Lifespan for older affected individuals may not be affected.

The HEXB gene encodes the beta subunit of beta-hexosaminidase, which is needed for the formation of both hexosaminidase A (HEXA) and hexosaminidase B (HEXB) enzymes. These enzymes are needed for the breakdown of GM2 ganglioside. Accumulation of GM2 is toxic to cells in the body and central nervous system.

Patients with Sandhoff disease will have low total hexosaminidase activity (both hexosaminidase A and hexosaminidase B). Genetic testing is indicated to confirm the diagnosis, to determine carrier status, and to provide prenatal diagnosis.

For patients with a clinical and biochemical diagnosis of Sandhoff disease, approximately 96% will have two pathogenic variants detected in HEXB.

Pathogenic variants in the HEXB gene are inherited in an autosomal recessive manner.

Incidence in the general population is 1 in 300,000. Several population isolates in northern Argentina, Saskatchewan, and Cyprus have been identified with higher prevalence.

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