Tay-Sachs Disease
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Tay-Sachs Disease
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Authors: Michael Cole, MD; Sreenath Thati Ganganna, MBBS, MD 
University of Iowa, Stead Family Children’s Hospital, Iowa City, IA  

 Reviewed: July 2022

SUMMARY

Tay-Sachs disease (TSD) is a rare neurological disease in which the functions of the nervous system continually get worse. As the disease progresses, symptoms eventually include:

  • A loss of intentional movement 
  • Blindness 
  • Seizures 
  • A loss of purposeful interactions 
  • Death 

The most common form of TSD is diagnosed early in the first year of life. Sometimes the symptoms can start in older children or adults.  

TSD is a genetic disease caused by a change in the HEXA gene. The change causes a lack of an enzyme called beta-hexosaminidase A. This enzyme is normally present inside the nerve cells of the brain. It helps to break down and recycle molecules called gangliosides. When this enzyme is lacking, the gangliosides build up and cause damage to brain cells.  

TSD occurs in about 1 in 320,000 live births in the United States overall. However, it is more common in those with certain types of heritage, including:

  • Ashkenazi Jewish 
  • French Canadian 
  • Pennsylvania Dutch 
  • Louisiana Cajun 

Males and females are affected equally. 

The disease is lifelong and shortens the lifespan. There is no known cure. Most children who have symptoms in infancy will die by age 5.  

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Disorder Overview

DESCRIPTION

TSD is a severe neurological disease that gets worse over time. It usually begins within the first few months of life. It causes a rapid decline in babies’ ability to think, move, eat, and breathe.

Subtypes of Tay-Sachs Disease 

There are three subtypes of TSD. Each subtype first appears at a different stage of life. 

Infantile-Onset TSD (Classic TSD)

Most people with TSD have this subtype.  Children often appear normal in the first few months of life. However, low muscle tone can be seen at birth. 

Symptoms usually begin at around 3 to 6 months old, with:

  • Delayed development or loss of developmental milestones 
  • Low muscle tone, or floppiness (hypotonia) 
  • Abnormal jerking movements (myoclonus)  
  • Progressive weakness 

During the first year of life, symptoms progress quickly and can include:

  • Muscle tightness causing stiffening of arms and legs (spasticity) 
  • Increased or jumpy reflexes when tapped at the joints (hyperreflexia) 
  • Decreased purposeful movements of the arms and legs 
  • Decreased alertness and responsiveness to surroundings  
  • Sleep difficulties 
  • Irritability  
  • Seizures 
  • Vision loss

By 18 months, a child’s head size becomes abnormally large, a condition called macrocephaly. By 2 years old, children with TSD:

  • Have difficulty swallowing 
  • Are unable to move their arms and legs 
  • Can be unresponsive to their environment (also known as a vegetative state) 
  • Have breathing difficulty that worsens over time

This difficulty breathing increases the risk of life-threatening respiratory infections. Death usually occurs from respiratory complications by age 5.

Juvenile-Onset TSD (Juvenile GM2 Gangliosidosis)

The juvenile-onset form of TSD involves relatively normal development in early childhood. Symptoms start between ages 2 and 5 years old. Early symptoms include: 

  • Gradual loss of developmental milestones 
  • Weakness 
  • Difficulty walking 
  • Lack of coordination 
  • Slurred speech (dysarthria)

Over time, the symptoms get worse and can include:

  • Worsening muscle tightness or stiffness (spasticity) 
  • Loss of the ability to walk 
  • Loss of the ability to speak 
  • A decline in memory, intelligence, and problem-solving abilities.  
  • Vision problems (including blindness)
  • Seizures 

Eventually, patients experience a decreased responsiveness to surroundings. A vegetative state occurs between the ages of 10 and 15. Respiratory complications lead to death by age 15.

Late- or Adult-Onset TSD (Late-Onset GM2 Gangliosidosis)

The late-onset form of TSD can occur any time between the late teenage years and adulthood. The type and severity of symptoms of this subtype vary dramatically. This subtype progresses more slowly. Symptoms can include:

  • Weakness that gets worse over time 
  • A wasting or loss of muscles 
  • Difficulty coordinating movements or imbalance while walking (ataxia) 
  • Muscle twitching (fasciculations) and cramping 
  • Tremors of the arms and legs 
  • Difficulty swallowing (dysphagia) 
  • Difficulty walking 
  • Psychiatric symptoms, such as anxiety or depression
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SIGNS AND SYMPTOMS

Stages of Tay-Sachs Disease

The earliest symptoms of TSD usually involve: 

  • Weakness 
  • Abnormal movements of the arms and legs 
  • An excessive startle response

During the middle stages of TSD, development stops and children lose skills. Over time, they can develop seizures and blindness.

Eventually, the symptoms are so severe that children cannot interact with their surroundings. They become so weak that they cannot move purposefully. Severe muscle weakness can cause breathing problems and high risk of respiratory infections.  

Important Symptoms

Some of the most important symptoms of TSD include:

Low muscle tone (hypotonia).

Muscle tone is the normal tension present in resting muscles. Low muscle tone in children with TSD is one of the first symptoms of the disease. This can result in: 

  • An inability to hold the head up 
  • Loose or floppy arms and legs

Exaggerated startle response.

Children with TSD can startle very easily. A startle can happen in response to minor stimulation, like noises or light. This is an important early symptom that helps doctors think of Tay-Sachs disease as a possible diagnosis.

Abnormal movements.

Children with TSD frequently have sudden, short jerking movements in a muscle or group of muscles. These movements are not purposeful. This is known as myoclonus.

Abnormal reflexes.

Children with TSD have abnormally increased reflexes known as hyperreflexia. A child’s doctor may be able to see brisk or jumpy muscle contractions when they tap on the child’s knees, elbows, or ankle joints. This is evidence of damage to the brain or spinal cord.

Seizures.

Seizures often begin by 12 months of age. These seizures can be hard to control. They can require treatment with multiple antiseizure medications. Many types of seizures can be present, including:  

  • Tonic-clonic seizures (with a whole-body shaking) 
  • Myoclonic seizures (with a sudden, brief jerking of the arm or the legs) 
  • Tonic seizures (with whole body stiffening) 
  • Absence seizures (with staring or unresponsiveness)

Vision loss.

TSD also causes progressive vision loss. At age 6 months, a “cherryred spot” occurs as a result of swelling at the back of the eye. This can be easily seen by an ophthalmologist (an eye doctor) or a neurologist (a brain doctor). By age 12 to 18 months, some vision loss will have occurred. By 30 months, most children are blind.

CAUSES

TSD happens because of an abnormal change (a mutation) in a gene called HEXA. There are at least 130 mutations of HEXA that have been identified. All of these mutations cause a deficiency of an enzyme called beta-hexosaminidase A. This enzyme is normally present inside the nerve cells of the brain. It helps to break down and recycle molecules called gangliosides. When this enzyme is missing, the gangliosides build up and cause damage to the brain cells.  

Sometimes the enzyme is missing completely. A complete lack of the enzyme causes infantile-onset TSD. Other times, the enzyme is only reduced. A partial lack of the enzyme leads to juvenile- or late-onset TSD. 

Inheritance in TSD 

TSD is an inherited genetic disease. People with TSD have parents who carry the genetic mutation but are not affected by it. TSD is inherited as an autosomal recessive condition. This means that one abnormal copy of the gene comes from each parent. If two parents who are carriers have a child:

  • There is a 1 in 4 chance the child will have TSD 
  • There is a 2 in 4 chance the child will become a carrier, but not develop TSD 
  • There is a 1 in 4 chance the child will not be a carrier or have the disease  

Around 1 in 300 people carry a HEXA mutation. They have 1 normal copy and 1 abnormal copy of the HEXA gene. TSD appears in around 1 in 320,000 people in the United States.

Risk Factors

The risk of having the TSD is the same in males and females. However, some people are at higher risk of being carriers or having the disease. For example, in the Ashkenazi Jewish population, around 1 in 30 people are carriers of a HEXA mutation. TSD occurs in around 1 in 3500 births.  

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LABORATORY INVESTIGATIONS

Steps for Diagnosis 

There are several steps to making a diagnosis of TSD.

1. Neurological and eye exam.

The first step is a neurological exam. This can identify common TSD findings, including:

  • Low muscle tone 
  • Abnormal reflexes 
  • Exaggerated startle response 
  • Loss of developmental milestones

A doctor may also recommend an eye exam at this early stage. An eye exam can look for a classic sign called a “cherry-red spot” in the retina.

2. Blood tests.

The next step is a blood test to measure levels of the enzyme made by the HEXA gene. Children with infantileonset TSD usually have very low levels of the enzyme, up to 5% of normal. People with juvenile or lateonset forms usually have 10% to 15% of normal.

3. Magnetic resonance imaging (MRI).

A brain MRI is not an essential test for making the diagnosis of TSD. However, it can be helpful if it identifies abnormal bright spots or patches in certain regions of the brain. If these spots or patches appear in the basal ganglia or white matter, it is a sign of TSD.

4. Genetic testing.

A child’s doctor may order specific genetic tests. These tests can look for the most common variations in the HEXA gene that can cause TSD.

Prenatal Testing for Tay-Sachs Disease

Parents can be tested before having a baby to see if they are carriers of TSD. Testing can also be performed on fetal cells in the womb using one of two methods: 

  • Chorionic villus sampling (taking a small sample of the placenta) 
  • Amniocentesis (using a needle to remove a small amount of the amniotic fluid)
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TREATMENT AND THERAPIES

Experimental Treatments 

There is no known cure for TSD. Several treatments are currently being studied. However, these are not approved for routine use. They are only used experimentally. These experimental treatments include:

  • Enzyme replacement therapy: Replacing deficient beta-hexosaminidase A  
  • Gene therapy: Replacing an abnormal HEXA gene with a normal version 
  • Substrate reduction therapy: Decreasing ganglioside build-up in the brain 
  • Bone marrow transplantation 

Supportive Care

Because there is no known cure, most of the treatments for TSD focus on managing the symptoms. In particular, they focus on managing the problems that can occur with progressive weakness. These include problems with eating and breathing:

  • Problems with eating. Children with TSD can have trouble swallowing food. This increases the risk of aspiration (food or liquid going into the lungs) and pneumonia. Because of these symptoms, some children need to have a feeding tube placed. It may go through the nose, down the throat, and into the stomach, or it may be surgically placed directly into the stomach. This helps the child receive enough nutrition safely. It decreases the risk of early death due to respiratory failure and infection. 
  • Problems with breathing. Children with TSD can have respiratory muscle weakness. They may have trouble coughing up secretions or mucus from the lungs and airways. This may require special chest physical therapy to help clear the secretions and lower the risk of pneumonia.

Treating Seizures

Seizures are very common in TSD and can be very difficult to control. Controlling seizures can require the use of several antiseizure medications at once. In some cases, the seizures cannot be controlled despite treatment with multiple antiseizure medicines.

Treatment Team

A TSD treatment team may consist of:

  • A neurologist (a brain/nerve doctor) 
  • A pulmonologist (a lung doctor) 
  • A gastroenterologist (a doctor for the digestive system) 
  • A physical therapist 
  • An occupational therapist 
  • A speech therapist 
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OUTLOOK

Tay-Sachs disease is a neurodegenerative, progressive disease. This means that it gets worse over time. It does not currently have a cure. The infantile-onset form of the disease is the most common form. In it, death usually occurs by age 4 or 5. 

In the juvenile-onset form of the disease, death usually occurs by age 10 or 15. In the late-onset form, patients usually have a more typical lifespan.

A diagnosis of TSD can have a significant impact on families. Affected children do not develop the ability to care for themselves. From the time of diagnosis, this is a disease that requires frequent doctor visits. Children have an increased risk of hospitalization. As the disease progresses, it can require parents to understand the use of some medical devices (such as a feeding tube). In many cases, additional home services like home nursing are needed.

Resources 

National Tay-Sachs & Allied Diseases Association

National Tay-Sachs & Allied Diseases Association (NTSAD) leads the worldwide fight to treat and cure Tay-Sachs by driving research, forging collaboration, and supporting families. NTSAD provides compassionate support, helpful resources, an annual family conference, support for siblings, and a monthly family newsletter. Find information about Tay-Sachs research and the NTSAD Research Initiative on the Research page. NTSAD has a private Facebook group for affected individuals and their families. You can request to join the NTSAD Family Support Group on Facebook by filling out this form. 

Childhood Stroke 1

Child Neurology Foundation (CNF) solicits resources from the community to be included on this webpage through an application process. CNF reserves the right to remove entities at any time if information is deemed inappropriate or inconsistent with the mission, vision, and values of CNF. 

Research 

ClinicalTrials.gov for Tay-Sachs Disease (birth to 17 years).

These are clinical trials that are recruiting or will be recruiting. Updates are made daily, so you are encouraged to check back frequently. 

ClinicalTrials.gov is a database of privately and publicly funded clinical studies conducted around the world. This is a resource provided by the U.S. National Library of Medicine (NLM), which is an institute within the National Institutes of Health (NIH). Listing a study does not mean it has been evaluated by the U.S. Federal Government. Please read the NLM disclaimer for details.    

Before participating in a study, you are encouraged to talk to your health care provider and learn about the risks and potential benefits.

Family Stories

If your family is now faced with the diagnosis of Tay-Sachs disease, know that you are not alone. The National Tay-Sachs & Allied Diseases Association (NTSAD) shares pictures of some of the people who are impacted by Tay-Sachs on their We Care for Rare page.

The information in the CNF Child Neurology Disorder Directory is not intended to provide diagnosis, treatment, or medical advice and should not be considered a substitute for advice from a healthcare professional. Content provided is for informational purposes only.  CNF is not responsible for actions taken based on the information included on this webpage. Please consult with a physician or other healthcare professional regarding any medical or health related diagnosis or treatment options. 

References

Lew RM, Burnett L, Proos AL, Delatycki MD, Tay-Sachs disease: current perspectives from Australia. Appl Clin Genet. 2015 Jan 21;8:19-25. https://doi.org/10.2147/TACG.S49628. PMID: 25653550 

Lopez Vasquez, K. Tay-Sachs Disease. J Neonatal Nursing. 2020 Mar;26(6): 316-318. https://doi.org/10.1016/j.jnn.2020.02.001. 

Ramani PK, Parayil Sankaran B. Tay-Sachs Disease. 2021 Nov 5. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. PMID 33232090.  

Toro C, Shirvan L, Tifft C. HEXA Disorders. 1999 Mar 11 [Updated 2020 Oct 1]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. PMID: 20301397. 

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