Introductory Remarks
What is Tay-Sachs disease?
Tay-Sachs disease is a genetic condition which affects the neuronal cells in the brain and spinal cord of a person (child). It causes damage and death of these crucial cells. It is progressive, does not have a definitive cure and can lead to early death. With proper treatment strategies, the child can be kept comfortable. This condition is also referred to as GM2 gangliosidosis or hexaminidase A deficiency.
Tay-Sachs disease is an autosomal recessive genetic disease. It is a type of GM2 gangliosidosis and sphingolipidosis.
Essential Statistics and Key Facts
- The usual onset for Tay-Sachs disease is usually 3-6 months of age.
- There are three kinds of Tay-Sachs disease and this classification is based on when the symptoms develop:
- Classic infantile Tay-Sachs disease.
- Juvenile Tay-Sachs disease.
- Late-onset Tay-Sachs disease.
- Its is estimated that 1 out of 300 individuals possess the genetic mutation which is responsible for development of Tay-Sachs disease.
- This disease has been named after Waren Tay and Bernard Sachs.
- Waren Tay was a British ophthalmologist whereas Bernard Sachs was an American neurologist.
- Tay, in1881, first described a symptomatic red spot on the retina of the eye.
- Sachs on the other hand is remembered for describing the cellular changes and noting an increased rate of disease among the Ashkenazi Jews.
- Approximately 1 in 23,600 Ashkenazi Jews are affected at birth.
Causal Factors
What are the causes of Tay-Sachs disease?
Tay-Sachs disease is caused by a genetic mutation in the HEXA gene. This gene is located on chromosome 15 and it codes for hexaminidase A, a sub-unit of enzyme hexaminidase. Hexaminidase breaks down toxins in the body.
The mutation disrupts activity of the enzyme leading to GM2 ganglioside molecule building up within the cells, and this leads to toxicity.
In the absence of hexaminidase A, fatty substances collect in the cells leading to damage and destruction of the brain and the spinal cord. This leads to symptoms of Tay-Sachs disease.
Tay-Sachs carrier
This is an individual who has one functional copy of the HEXA gene and one copy which has the disease-causing variant.
Human beings inherit 2 gene copies, one from each biological parent to form a pair. Carriers, usually do not have the condition nor do they present any symptoms of Tay-Sachs disease because their bodies can depend on one functional gene.
When 2 individuals who carry the genetic variant get an offspring, the child’s risk of developing the condition can be stated as follows:
- 25% chance that the child will not inherit any variant HEXA genes, therefore will not have Tay-Sachs disease, neither will he or she be a carrier.
- 50% likelihood that the child inherits a variant from either of the parents, and therefore the child becomes a carrier. Being a carrier, he or she can pass it on to their offspring.
- 25% chance that the child receives variant genes from both parents and will have Tay-Sachs disease.
Risk Elements
What are the risk factors for Tay-Sachs disease?
- If both biological parents carry the genetic variant responsible for Tay-Sachs disease, then the offspring is at risk.
- There is an increase risk among the following people:
- Eastern Europeans.
- Ashkenazi Jews.
- French-Canadians.
- Among the above mentioned, approximately 1 in 30 individuals carry the genetic variant.
Types
What are the types of Tay-Sachs disease?
- There are three types of Tay-Sachs disease.
- This categorization is based on when the symptoms develop.
- These are:
- Classic infantile Tay-Sachs disease.
- Juvenile Tay-Sachs disease.
- Late-onset Tay-Sachs disease.
Classic infantile Tay-Sachs disease
It is the most common form. Children usually start developing symptoms at 6 months.
Juvenile Tay-Sachs disease
It is a very rare type. Children develop symptoms between age of 5 years and their teenage years.
Late-onset Tay-Sachs disease
- Just as juvenile form, it is also very rare.
- Symptoms develop during late teen age or early adulthood or sometimes even after an individuals reaches 30 years old.
- It may not affect the life expectancy of an individual.
Signs & Symptoms Overview
How does Tay-Sachs disease manifest?
Classic infantile Tay-Sachs disease;
Early symptoms (at around 6 months of age) include:
- Being easily startled by loud noises.
- Difficulty sitting.
- Muscle weakness.
Before 1 year of age, symptoms include:
- Seizures.
- Loss of hearing.
- Cherry-red spot on the eyes.
- Dysphagia (difficulty swallowing).
- Involuntary muscle twitching.
- Respiratory infections.
- Loss of vision.
Around 2 years old:
- Unresponsive state due to poor brain function.
- Death which occurs between 2-4 years is often caused by pneumonia.
Juvenile Tay-Sachs disease;
The following symptoms may be experienced at the age of 5 years:
- Seizures.
- Loss of hearing.
- Loss of vision.
- Frequent infections.
- Difficulty with speech.
- Loss of muscle control.
- Mood changes.
- Behavioral changes.
- Loss of previously learned skills.
This condition progresses into teenage years.
It leads to early death during the teenage years.
Late-onset Tay-Sachs disease;
In adults.
The symptoms are:
- Dysphagia.
- Muscle weakness and spasms.
- Loss of coordination or ability to walk properly.
- Psychosis.
Note that in late-onset Tay-Sachs disease, the life expectancy of an individual is unaffected.
Diagnostic Procedures
How is Tay-Sachs disease diagnosed?
Blood tests.
- A blood sample is obtained from a child’s vein in their arm and the level of hexaminidase A in the sample is measured.
- This protein is mostly or completely absent in a child with classic infantile Tay-Sachs disease.
- Low levels have been identified in persons diagnosed with other forms of the disease.
Eye examination.
Your heath-care provider or an ophthalmologist may perform an eye exam to check and see if the child has classic cherry-red spot in the eye (classic infantile Tay-Sachs disease).
Tay-Sachs disease Diagnosis in pregnancy
- Specialized tests for diagnosing Tay-Sachs disease in pregnancy are:
- Amniocentesis.
- Chorionic villus sampling.
- Both test check for hexaminidase A and its level in the sample. Below-average levels signify Tay-Sachs disease.
- Genetic testing can be done on the samples obtained through amniocentesis and chorionic villus sampling to identify a mutation in the HEXA gene, which is responsible for Tay-Sachs disaese.
Treatment & Management
Is there a cure for Tay-Sachs disease?
No. Currently, Tay-Sachs disease does not have a cure.
Then, how is Tay-Sachs disease treated?
For classic infantile Tay-Sachs disease and juvenile Tay-Sachs disease, treatment is based on the presenting symptoms of the child. For example, prescribing ,medications to treat seizures.
Other treatment measures include:
- Proper nutrition.
- Hydration.
Late-onset Tay-Sachs disease treatment
- In these adults, treatment is aimed at ,managing the symptoms present.
- Medications to manage ;
- Muscle spasms.
- Mental health conditions.
- Using mobility equipment such as wheelchair to aid in navigation.
- Speech therapy.
- Supportive care and psycho-social support are also treatment strategies.
- Researchers are looking at enzyme replacement therapy as a possible treatment.
Differential Diagnosis
What are some of the differential diagnoses?
- Neuronal ceroid lipofuscinoses.
- Sandhoff disease.
- Leigh syndrome.
Complications
What is the complication of Tay-Sachs disease?
Death. Early death among children.
Preventive Strategies & Recommendations
What are the methods of preventing Tay-Sachs disease?
- There are no known methods of preventing Tay-Sachs disease.
- It is highly advised that a couple should get to know about the likelihood of them getting a baby with genetic conditions such a Tay-Sachs disease.
- They should therefore visit specialists for:
- Preconception counseling.
- Genetic testing.
- Apart from genetic testing and preconception counseling , prioritizing awareness campaigns and mass education can help to lower the frequency of the condition among at-risk populations.