DNA icon

Sandhoff Disease via the HEXB Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
HEXB 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7891HEXB81479 81479,81479 $990 Order Options and Pricing

Pricing Comments

Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Jana Paderova, PhD

Clinical Features and Genetics

Clinical Features

Sandhoff disease, also called GM2 Gangliosidosis Type II, is a neurodegenerative lysosomal storage disorder due to deficiency in both beta-hexosaminidase A and B isoenzymes. It is characterized by the accumulation of GM2 ganglioside, particularly in the brain, and by the storage of related glycolipids in the brain and in visceral organs (Sandhoff et al. 1971). Sandhoff disease is clinically heterogeneous. Three distinct clinical forms are recognized on the basis of age of onset of symptoms, clinical features, and disease progression (Kolter and Sandhoff 2006; Gravel et al. 2001).

1) Infantile Sandhoff disease, like Infantile Tay-Sachs disease, is characterized by onset before the age of 6 months, rapid progression and death by 4 years of age. Symptoms begin with a cherry-red spot in the macula, visual abnormalities, seizures, decline of physical and mental abilities and progress to blindness, deafness, paralysis and difficulty to swallowing. Unlike Tay-Sachs disease, organomegaly and slight bone deformation may occur in Sandhoff disease.

2) Juvenile Sandhoff disease is clinically heterogeneous. It is distinguished by onset of symptoms between 3-10 years of age. Clinical features include cerebellar ataxia, loss of movement coordination, progressive spasticity, dystonia, slow deterioration of speech, gait and posture, and cerebellar atrophy. Vision is spared. Death occurs in the early twenties.

3) Adult Sandhoff disease is also clinically heterogeneous. It is characterized by age of onset ranging from adolescence to adulthood, and slow progression. Symptoms include seizures, unsteady gait, cognitive loss, deterioration of speech, and psychosis.

The prevalence of Sandhoff disease has been estimated at 1 in 300,000 births in the general population. Unlike Tay-Sachs disease, Sandhoff disease is rare in the Ashkenazi Jewish population, with a prevalence rate estimated at 1 in 1,000,000 (Gravel et al. 2001).


Sandhoff Disease is inherited in an autosomal recessive manner and results from pathogenic variants in the HEXB gene (Bikker et al. 1989; Nakano and Suzuki 1989). It occurs worldwide, with a carrier frequency of 1/278 in the general population, and 1/500 in the Ashkenazi Jewish population (Gravel et al. 2001).

Over 80 pathogenic variants have been reported and include missense, nonsense, splicing, small insertions/deletions and several large deletions. Pathogenic variants have been shown to arise throughout the HEXB gene and were documented in patients from various ethnic and geographic backgrounds such as South Americans (Kleiman et al. 1994), Japanese (Fujimaru et al. 1998), Italian (Zampieri et al. 2009), Arabs from the Middle East (Kaya et al. 2011), Iranians (Aryan et al. 2012), Spanish (Gort et al. 2012), and French (Gaignard et al. 2013).

The HEXB gene encodes the beta-subunit of beta-hexosaminidase A and B isoenzymes, which catalyze the biodegradation of GM2 gangliosides.

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the HEXB gene have been documented in the vast majority of patients with clinical features of GM2 gangliosidosis and deficiency of both beta-hexosaminidase A and B isoenzymes activities in plasma or cultured fibroblasts (Zampieri et al. 2009; Kaya et al. 2011; Aryan et al. 2012).

Several large pathogenic deletions have been reported in the HEXB gene. One of these, a 16-kb deletion spanning the first five exons, accounts for about 27% of pathogenic HEXB variants in patients from various ethnic and geographic origins (Neote et al. 1990). This deletion represents about 50% of pathogenic variants in Iranian patients with Sandhoff disease (Aryan et al. 2012).

Testing Strategy

This test provides full coverage of all coding exons of the HEXB gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

This test is indicated for patients with symptoms suggestive of GM2 gangliosidosis and reduction or deficiency of both beta-hexosaminidase A and B isoenzyme activities measured in plasma or cultured skin fibroblast; and family members of patients with known pathogenic variants in the HEXB gene. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in HEXB.


Official Gene Symbol OMIM ID
HEXB 606873
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Sandhoff Disease AR 268800

Related Tests

GM2-Gangliosidosis Variant AB via the GM2A Gene
Tay-Sachs Disease via the HEXA Gene


  • Aryan H, Aryani O, Banihashemi K, Zaman T, Houshmand M. 2012. Novel Mutations in Sandhoff Disease: A Molecular Analysis among Iranian Cohort of Infantile Patients. Iran J Public Health 41:112-118. PubMed ID: 23113155
  • Bikker H, van den Berg FM, Wolterman RA, de Vijlder JJ, Bolhuis PA. 1989. Demonstration of a Sandhoff disease-associated autosomal 50-kb deletion by field inversion gel electrophoresis. Hum Genet 81:287-288. PubMed ID: 2921040
  • Fujimaru M, Tanaka A, Choeh K, Wakamatsu N, Sakuraba H, Isshiki G. 1998. Two mutations remote from an exon/intron junction in the beta-hexosaminidase beta-subunit gene affect 3'-splice site selection and cause Sandhoff disease. Hum Genet 103:462-469. PubMed ID: 9856491
  • Gaignard P, Fagart J, Niemir N, Puech JP, Azouguene E, Dussau J, Caillaud C. 2013. Characterization of seven novel mutations on the HEXB gene in French Sandhoff patients. Gene 512:521-526. PubMed ID: 23046579
  • Gort L, de Olano N, Macías-Vidal J, Coll MA; Spanish GM2 Working Group. 2012. GM2 gangliosidoses in Spain: analysis of the HEXA and HEXB genes in 34 Tay-Sachs and 14 Sandhoff patients. Gene 506:25-30. PubMed ID: 22789865
  • Gravel RA, Kaback MM, Proia RL, Sandhoff K, Suzuki K and Suzuki K. 2001. The GM2 Gangliosidoses.  In: Scriver et al. Eds 8 Vol 3 McGraw-Hill, New York, 3827-3877.
  • Kaya N, Al-Owain M, Abudheim N, Al-Zahrani J, Colak D, Al-Sayed M, Milanlioglu A, Ozand PT, Alkuraya FS. 2011. GM2 gangliosidosis in Saudi Arabia: multiple mutations and considerations for future carrier screening. Am J Med Genet A 155A:1281-1284. PubMed ID: 21567908
  • Kleiman FE, de Kremer RD, de Ramirez AO, Gravel RA, Argaraña CE. 1994. Sandhoff disease in Argentina: high frequency of a splice site mutation in the HEXB gene and correlation between enzyme and DNA-based tests for heterozygote detection. Hum Genet 94:279-282. PubMed ID: 8076944
  • Kolter T and Sandhoff K. 2006. Sphingolipid metabolism diseases. Biochim Biophys Acta 1758:2057-79. Review. PubMed ID: 16854371
  • Nakano T and Suzuki K. 1989. Genetic cause of a juvenile form of Sandhoff disease. Abnormal splicing of beta-hexosaminidase beta chain gene transcript due to a point mutation within intron 12. J Biol Chem 264:5155-5158. PubMed ID: 2522450
  • Neote K, McInnes B, Mahuran DJ, Gravel RA. 1990.  Structure and distribution of an Alu-type deletion mutation in Sandhoff disease. J Clin Invest. 86:1524-1531. PubMed ID: 2147027
  • Sandhoff K, Harzer K, Wässle W, Jatzkewitz H. 1971. Enzyme alterations and lipid storage in three variants of Tay-Sachs disease. J Neurochem 18:2469-89. PubMed ID: 5135907
  • Zampieri S, Filocamo M, Buratti E, Stroppiano M, Vlahovicek K, Rosso N, Bignulin E, Regis S, Carnevale F, Bembi B, Dardis A. 2009. Molecular and functional analysis of the HEXB gene in Italian patients affected with Sandhoff disease: identification of six novel alleles. Neurogenetics 10:49-58. PubMed ID: 18758829


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

loading Loading... ×


An error has occurred while calculating the price. Please try again or contact us for assistance.

View Ordering Instructions

1) Select Test Method (Platform)

1) Select Test Type

2) Select Additional Test Options

No Additional Test Options are available for this test.

Note: acceptable specimen types are whole blood and DNA from whole blood only.
Total Price: loading
Patient Prompt Pay Price: loading
A patient prompt pay discount is available if payment is made by the patient and received prior to the time of reporting.
Show Patient Prompt Pay Price
Copy Text to Clipboard