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
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.
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.
3. Magnetic resonance imaging (MRI).
4. Genetic testing.
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)
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
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
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.
