Tay-Sachs disease is an inherited genetic disorder. It occurs due to an error in a specific gene that is responsible for the creation of an enzyme (called HEXA) that breaks down fatty substances called gangliosides. Gangliosides are commonly found in the nervous system and help cells communicate with each other. With this gene mutated, HEXA does not form correctly and cannot do its job of breaking gangliosides down. This leads to an accumulation of gangliosides in the brain and spinal cord which stops the nerves from working properly, and is usually fatal.

The increased risk of Tay-Sachs disease can be assessed through genetic screening of the parents. There is no cure for Tay-Sachs disease, and treatment involves controlling symptoms and making life with the disease as comfortable as possible.

Types of Tay-Sachs disease and symptoms

Infantile Tay-Sachs: this usually presents around 3-6 months of age, with life expectancy only being a few years. This is the most common form.¹

Symptoms include:

• “Cherry red” spots in eyes
• Loss of motor skills
• Muscle weakness, leading to paralysis
• Seizures
• Swallowing problems
• Growth in head size
• Loss of vision and hearing

Juvenile Tay-Sachs: develops in childhood with survival expected into teenage years, and is less common.

Symptoms include:

• Behavioural problems
• Gradual loss of movement control
• Frequent respiratory infections
• Seizures
• Gradual loss of vision and hearing
• Declining mental function

Adult onset Tay-Sachs: begins in late childhood or early adulthood; this does not necessarily impact life expectancy, and symptoms progress slowly. It is the rarest form of Tay-Sachs.²

Symptoms include:

• Loss of coordination
• Muscle weakness
• Tremors and muscle spasms
• Loss of ability to walk
• Issues with speaking and swallowing

Causes

Tay-Sachs disease is an inherited genetic disorder that occurs when a child inherits two mutated genes from the parents, causing the child to present with the disease. The parents may not have Tay-Sachs, and only carry a single faulty gene. The mutation that causes the disorder occurs in the HEXA gene, which is responsible for the production of the hexosaminidase A (HEXA) enzyme. The proper functioning of the HEXA gene results in the production of the HEXA enzyme, which breaks down gangliosides. When the HEXA gene is mutated, the enzyme can be inefficient, faulty or entirely absent; when this occurs, gangliosides can build up in the brain and nerve cells.³

People with a family history of Tay-Sachs disease are more likely to pass on the defective gene that causes Tay-Sachs and, therefore, the chance of a defective gene pair that results in the presentation of Tay-Sachs disease. Those of Ashkenazi Jewish heritage are at a higher risk of carrying the defective gene.¹ 

Diagnosis of Tay-Sachs disease

To diagnose Tay-Sachs, a healthcare professional will assess the symptoms experienced as well as any information about a family history of Tay-Sachs Disease. This can then be supported through various tests.

Blood tests can be used to diagnose Tay-Sachs. Low or no HEXA activity may be seen in individuals with Tay-Sachs disease. The blood test may also show increased levels of an enzyme called HEXB activity in relation to HEXA.

Genetic screening can also identify any potential changes to the HEXA gene that may be the cause of Tay-Sachs disease.

An eye exam can show a cherry red spot in the back of the eyes, which is a symptom of Tay-Sachs.

Prenatal testing can help diagnose Tay-Sachs before birth and prepare parents and doctors for a child born with Tay-Sachs disease. Chronic villus sampling (testing of a piece of the placenta) or amnioscentecis (testing of a sample of amniotic fluid) can assess a foetus’s genes to discover any issues with the HEXA gene, and diagnose Tay-Sachs disease.⁴ 

Imaging techniques can be used to identify damage caused by Tay-Sachs to the central nervous system. MRI and CT scanning can be useful tools for quantifying and detecting neuronal damage.⁵ 

Treatment

Tay-Sachs is an incurable genetic disease. Treatment involves managing symptoms (such as seizures and loss of muscle control) through pharmaceuticals and physiotherapy. The objective is to make the patient's life as comfortable as possible.

Future of diagnosis and treatment

Continuing advances in genetic sequencing and next-generation sequencing are providing increasingly accurate and timely gene sequencing and diagnosis of genetic disorders. Methods for gene therapy are being developed to counter the mutated HEXA gene and increase low HEXA enzymes in those affected by Tay-Sachs.⁶ 

Summary

Tay-Sachs disease is an inherited genetic condition that occurs due to a mutated HEXA gene. This mutation causes a reduction or complete absence of the HEXA enzyme, which is responsible for removing gangliosides from neural cells. In Tay-Sachs disease, this enzyme is not present or is deffective, causing a build of gangliosides in the brain and other parts of the central nervous system. This reduces the ability for proper neural signalling and is fatal in its classic type.

Genetic screening can discern whether the HEXA gene is mutated or not, and blood tests can be undertaken to quantify enzyme levels in the body, with low or no HEXA being diagnostic of Tay-Sachs disease.

Those of Ashkenazi Jewish descent have a higher risk of inheriting Tay-Sachs, and any family history is a risk factor for any potential birth.

Tay-Sachs disease is incurable, and treatment is focused on managing symptoms and making the affected person’s life as comfortable as possible. Research into gene therapy of the HEXA gene to combat Tay-Sachs is currently underway with the hope of advancing treatments for Tay-Sachs disease.