The key difference between Tay-Sachs and Sandhoff disease is that Tay-Sachs disease is a lysosomal storage disorder that is due to the deficiency of β-hexosaminidase A enzyme, while Sandhoff disease is a lysosomal storage disorder due to the deficiency of both β-hexosaminidase A and β-hexosaminidase B enzymes.
Gangliosides are complex sphingolipids present in the brain. There are two major forms: GM1 and GM2. Both these types may be involved in lysosomal storage disorders. GM2 gangliosidoses are a group of three related recessively inherited diseases where a deficiency of β hexosaminidase leads to the accumulation of GM2 ganglioside in the brain. These three diseases are better known by their individual names: Tay-Sachs disease, AB variant, and Sandhoff disease.
CONTENTS
1. Overview and Key Difference
2. What is Tay-Sachs Disease
3. What is Sandhoff Disease
4. Similarities – Tay-Sachs and Sandhoff Disease
5. Tay-Sachs vs Sandhoff Disease in Tabular Form
6. Summary – Tay-Sachs vs Sandhoff Disease
What is Tay-Sachs Disease?
Tay-Sachs disease is a lysosomal storage disorder that occurs due to the deficiency of the β-hexosaminidase A enzyme. It is an autosomal recessively inherited genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay-Sachs disease. This becomes apparent around three to six months when babies lose the ability to turn over, sit, or crawl. Later, this is followed by seizures, hearing loss, and inability to move, with death occurring by the age of three to five. The less common forms are the Tay-Sachs disease in later childhood or adulthood (juvenile or late-onset). These forms tend to be less severe. However, the juvenile form normally results in death by age 15. This disease has an ethnic association. It is rare in the general population. But in Ashkenazi Jews, French Canadians of southeastern Quebec, Old Order Amish of Pennsylvania, and Cajuns of southern Louisiana, this condition is more common.
Tay-Sachs disease is caused due to genetic mutation of the HEXA gene on chromosome 15. This gene encodes for a subunit of the β-hexosaminidase A enzyme. The mutation disrupts the enzyme activity, which results in the building up of GM2 ganglioside in the brain and spinal cord. This leads to toxicity. This condition can be diagnosed by measuring the blood β-hexosaminidase A level, microscopic analysis of the retinal neuron, and genetic testing. Furthermore, the possible treatments for Tay-Sachs disease include enzyme replacement therapy, substrate reduction therapy, increasing β-hexosaminidase A activity through the drug pyrimethamine, cord blood transplant, and gene therapy.
What is Sandhoff Disease?
Sandhoff disease is a lysosomal storage disorder that occurs due to the deficiency of both β-hexosaminidase A and β-hexosaminidase B enzymes. There is a combined β-.hexosaminidase A and B deficiency in this disease. The clinical manifestation of this disease includes progressive cerebral degeneration beginning at 6 months, which is accompanied by blindness, cherry-red macular spot, and hyperacusis. There are three types: the classic infantile form that occurs in 2 to 9 months of age, the juvenile form that occurs in children at age 3 to 10, and the adult form that occurs in older adults. Classic infantile form causes death by age 3, while juvenile form causes death by age 15. Moreover, it is not yet known whether this disease will cause a decrease in the life span of older adults. There is a visceral involvement (hepatomegaly and bone change) in this disease. However, there is no ethnic association for Sandhoff disease
The diagnosis of this disease can be made through testing the activity of β-hexosaminidase A and B (enzyme assays) and their levels in the blood. Genetic testing of the HEXB gene can also be used to confirm the diagnosis. The other diagnosis methods include liver biopsy, molecular analysis of cells and tissues to determine the presence of a genetic metabolic disorder, and urine analysis. Furthermore, the treatment options for Sandhoff disease may include using anticonvulsants to reduce seizures, consuming a precise diet, respiratory support for children, medications such as N-butyl deoxynojirimycin, and gene therapy.
What are the Similarities Between Tay-Sachs and Sandhoff Disease?
- Tay-Sachs and Sandhoff disease are two types of GM2 gangliosidoses.
- In both diseases, GM2 gangliosides accumulate in neuronal cells.
- Both diseases are due to the deficiency of two types of β-hexosaminidase
- They are genetic disorders inherited in an autosomal recessive pattern.
- Both diseases have three forms: infantile, juvenile, and adult-onset.
- They show similar common symptoms.
- Moreover, they can be treated through gene therapy.
What is the Difference Between Tay-Sachs and Sandhoff Disease?
Tay-Sachs disease is a lysosomal storage disorder that occurs due to the deficiency of β-hexosaminidase A enzyme while Sandhoff disease is a lysosomal storage disorder that occurs due to the deficiency of both β-hexosaminidase A and β-hexosaminidase B enzymes. Thus, this is the key difference between Tay-Sachs and Sandhoff disease. Furthermore, Tay-Sachs disease is due to the genetic mutation of the HEXA gene, while Sandhoff disease is due to the genetic mutation of the HEXB gene.
The below infographic presents the differences between Tay-Sachs and Sandhoff disease in tabular form for side by side comparison.
Summary – Tay-Sachs vs Sandhoff Disease
Tay-Sachs and Sandhoff disease are two types of lysosomal storage disorders that occur due to the accumulation of GM2 ganglioside. Tay-Sachs disease is due to the deficiency of β-hexosaminidase A enzyme, while Sandhoff disease is due to the deficiency of both β-hexosaminidase A and β-hexosaminidase B enzymes. So, this is the key difference between Tay-Sachs and Sandhoff disease.
Reference:
1. “Tay-Sachs Disease.” Healthline, Healthline Media, 3 Mar. 2022.
2. “Sandhoff Disease: What Is It, Causes, Diagnosis & Treatment.” Cleveland Clinic.
Image Courtesy:
1. “Sphingolipidoses” By Ebuxbaum, Sav_vas – Own work (CC BY-SA 3.0) via Commons Wikimedia