Tay-Sachs disease is a rare and usually fatal genetic disorder that causes progressive damage to the nervous system.
Symptoms usually begin before a baby is six months old. Their development slows down and they gradually lose their ability to move.
The most noticeable early symptoms include a baby being excessively startled by sudden noises and red dots appearing near the middle of their eyes.
The child then develops problems such as muscle weakness, loss of vision, loss of hearing and seizures.
Most children with the condition die before they're four years old.
Less common forms of Tay-Sachs disease can begin later in childhood or even early adulthood. These usually progress less rapidly, although it's usually fatal.
What causes Tay-Sachs disease?
Tay-Sachs disease is caused by a mutation in the HEXA gene. A genetic mutation is a permanent alteration in the DNA sequence that makes up a gene. It causes one or more processes of the body to not work properly.
A mutated HEXA gene results in the body not producing an enzyme called Hexosaminidase-A (Hex-A). Without this enzyme, a fatty substance called GM2 ganglioside builds up in the cells of the brain and nerves, and stops them working normally, eventually destroying them.
Both parents have to be carriers of a HEXA mutation to be at risk of having a child with Tay-Sachs disease. If both parents are carriers, their children will have a 25% chance of developing the condition.
Testing for Tay-Sachs disease
Screening for Tay-Sachs disease is recommended for people in high-risk groups before planning a family. In the UK, this includes people of Ashkenazi Jewish descent and anyone with a history of the condition in their family.
Screening can take place at two points, either before or after a baby is conceived. If the condition is diagnosed in an unborn baby, the parents can decide whether or not to continue with the pregnancy.
How is Tay-Sachs disease treated?
There's currently no cure for Tay-Sachs disease, so treatment involves making the child feel as comfortable as possible by treating the associated symptoms.
Research is being carried out into possible cures for Tay-Sachs disease, but this is still at an early stage.
Who is affected?
Tay-Sachs disease used to be most common in people of Ashkenazi Jewish descent. Most Jewish people in the UK are Ashkenazi Jews.
It's thought that around 1 in 25 Ashkenazi Jewish people are carriers of the mutated gene that causes Tay-Sachs disease.
However, with screening, the condition is now rare and most cases now occur in people who aren't of Ashkenazi Jewish descent. It's estimated that only about 1 in every 360,000 children born worldwide has Tay-Sachs disease.
Symptoms of Tay-Sachs disease
In the most common form of Tay-Sachs disease, classic infantile Tay-Sachs disease, a baby will develop normally until they're around three to six months old.
One of the first noticeable signs of the condition is the appearance of a red dot at the back of their eyes. You may also notice that their vision seems poor, or that they're excessively startled by noises and movement.
It's likely that your baby will be much slower in reaching developmental milestones, such as learning to crawl.
Additional symptoms usually develop after about eight months of age and quickly become more severe. They include:
increasing muscle weakness that progresses to paralysis
increasing loss of vision
loss of hearing
difficulties swallowing (dysphagia)
muscle stiffness (spasticity)
lack of interest in the world around them
repeated fits (seizures)
Children with Tay-Sachs disease become increasingly vulnerable to infection, particularly lung infections. Many children die from a complication of an infection such as pneumonia.
Most children with infantile onset Tay-Sachs disease die before they're four years old, because of complications from repeated infections.
Rarer forms of Tay-Sachs disease
There are two much rarer forms of Tay-Sachs disease.
In the juvenile form, the symptoms don't usually begin until a child is aged 2 to 10 years old.
Initially, problems develop with speech and motor skills, such as balance, walking and holding objects. Some children may also develop problems with vision.
As the condition progresses, the child will have repeated fits and experience dementia.
Most children with the juvenile form of Tay-Sachs disease eventually enter a vegetative state, where they're awake, but showing no signs of awareness. This usually happens between the ages of 10 and 15. The most common cause of death is a complication of an infection.
The symptoms of late-onset Tay-Sachs disease develop later in life, usually during the teenage years or early adulthood.
loss of balance and co-ordination
uncontrollable shaking of the hands (tremor)
muscle cramps and twitching
Around one in three people with late-onset Tay-Sachs disease also develop mental health conditions, such as bipolar disorder or psychosis. They may see or hear things that aren't there (hallucinations) or believe things that aren't true (delusions).
Unlike other forms of the condition, late-onset Tay-Sachs disease doesn't always shorten life expectancy.
Causes of Tay-Sachs disease
Tay-Sachs disease is caused by a genetic mutation in the HEXA gene.
This mutation affects the production of an enzyme called Hexosaminidase-A (Hex-A). Enzymes are proteins the body uses for chemical reactions.
The Hex-A enzyme plays a vital role in helping to remove a fatty substance called ganglioside from nerve cells. Without the Hex-A enzyme, ganglioside builds up inside these cells and they gradually stop functioning.
In most cases of Tay-Sachs disease, this enzyme is completely absent. However, in the rarer forms that develop later in life, the function of the enzyme is severely limited. This means it takes longer for ganglioside to damage the nerve cells.
The build-up of ganglioside in the nerve cells effects many bodily functions, including vision and hearing, speech, physical movement and mental functions.
How the mutation is inherited
All the genes in your body come in pairs. You receive one from your mother and the other half from your father.
It takes two copies of the mutated HEXA genes to cause Tay-Sachs disease, one from the mother and one from the father.
If you only receive one copy of the mutated gene from one of your parents, you won't develop Tay-Sachs disease. However, you'll be a carrier of the mutated gene.
If you're a carrier of a HEXA mutation and you have a baby with a partner who is also a carrier of a HEXA mutation, there's:
a 25% chance the baby will receive a pair of normal genes and won't develop the condition
a 25% chance the baby will receive a pair of mutated genes and will develop Tay-Sachs disease
a 50% chance the baby will receive one normal gene and one mutated gene, and will become a carrier of a HEXA mutation but won't develop the condition
It's estimated that around 1 in 250 people are carriers of the HEXA mutation.
Testing for Tay-Sachs disease
Tests can be carried out to check if you're a carrier of Tay-Sachs disease or to diagnose the condition after birth.
Screening for the HEXA mutation that causes Tay-Sachs disease is recommended if you're planning to start a family and you're in a high-risk group for developing the disease.
In the UK, two main groups of people are thought to have a high risk of developing the condition:
people of Ashkenazi Jewish descent – this applies to most people of Jewish descent in the UK
people with a known history of Tay-Sachs disease in their family
Screening involves checking yourself and your partner for the HEXA mutation using a blood test. If you both test positive, you have a 25% chance of conceiving a baby who develops Tay-Sachs disease.
It's also possible to test a foetus for Tay-Sachs disease during pregnancy (antenatal screening) using tests such as:
chorionic villus sampling (between weeks 11 and 14 of pregnancy) – where a sample of cells is taken from the placenta to be tested
amniocentesis (between weeks 15 and 20 of pregnancy) – where a needle is used to remove amniotic fluid for testing
If a diagnosis of Tay-Sachs disease is confirmed, you can choose to terminate or continue the pregnancy.
Tests after birth
A diagnosis of Tay-Sachs disease would be strongly suspected if a young baby develops symptoms closely associated with the condition, such as an exaggerated response to sudden noises and red spots at the back of the eyes.
Blood tests can also be carried out to check if the body is producing the Hexosaminidase-A (Hex-A) enzyme (see causes of Tay-Sachs disease for more information).
If there's any doubt about the diagnosis, it can usually be confirmed by taking a blood sample and extracting DNA from it to check for the HEXA mutation.
Receiving the diagnosis
Being told your baby has a fatal and incurable condition is a devastating experience, and you will probably experience profound feelings of grief, bereavement and even guilt.
The National Tay-Sachs & Allied Diseases Association is an American foundation for people affected by Tay-Sachs disease. Its website has information on ways to treat the symptoms, as well as useful advice about coping with the emotional impact of the condition.
The UK-based charity Genetic Alliance UK also provides information and services for people who have been affected by genetic conditions such as Tay-Sachs disease, as do organisations such as Climb.
Pre-implantation genetic diagnosis
For couples at risk of having a child with Tay-Sachs disease, pre-implantation genetic diagnosis (PGD) may be an option.
PGD involves using in vitro fertilisation (IVF), where eggs are removed from a woman's ovaries before being fertilised with sperm in a laboratory. After a few days, the resulting embryos can be tested for Tay-Sachs disease and a maximum of two unaffected embryos are transferred into the uterus.
However, funding for PGD is decided on an individual basis. For example, you may be considered ineligible for PGD if you already have unaffected children or if the chances of success are thought to be low. In these cases, you can choose to fund PGD yourself, although it's likely to cost between £6,000 and £10,000.
There are many reasons why people decide to have genetic tests. A geneticist explains what genetic testing involves, the reasons for having or not having it, and how to deal with a positive test result.
Treating Tay-Sachs disease
There's currently no cure for Tay-Sachs disease, so the aim of treatment is to make living with the condition as comfortable as possible.
Treatment usually focuses on:
preventing problems with the lungs and airways
relieving any feeding or swallowing problems (dysphagia)
using medication to help control or relieve symptoms, such as fits and muscle stiffness
Your child's care plan
Because of the rarity of Tay-Sachs disease, you'll usually be referred to a specialist centre that has experience of treating children with complex health needs, such as:
Birmingham Children's Hospital
Great Ormond Street Children's Hospital, London
St Mary's Hospital, Manchester
Children with Tay-Sachs disease can have complex needs. They'll need to be treated by a team of different specialists working together. These types of teams are called multidisciplinary teams (MDTs).
After the initial diagnosis, you and your child will probably need to spend some time at the specialist centre so a detailed treatment plan can be drawn up.
Once your child's symptoms stabilise, your MDT may be able to speak to your GP or local clinical commissioning group (CCG) so any necessary treatment can be given where you live. This will hopefully mean that you and your child only have to visit the centre occasionally.
Problems with the lungs and airways
Children with Tay-Sachs disease are more vulnerable to developing problems with their lungs and airways. This is because:
food or liquid can fall into the lungs and trigger an infection – this type of infection is called aspiration pneumonia
increasing muscle weakness can result in poor cough reflexes and a build-up of mucus in their lungs (congestion)
Children with Tay-Sachs disease are prone to drooling, and the excessive production of saliva can further disrupt breathing.
These difficulties are described in more detail below.
Aspiration pneumonia can be very difficult to prevent in children with Tay-Sachs disease.
Antibiotics are the most common treatment for aspiration pneumonia. Depending on how severe it is, this may be antibiotic tablets or injections. In severe cases, where airways become inflamed and swollen, a tube may be required to help keep the airways open.
Congestion of the lungs with mucus can usually be treated with chest physiotherapy (chest PT).
Chest PT involves several techniques, such as patting your child's chest to encourage their cough reflex. Chest PT should only be attempted if you've been properly trained, as performing it incorrectly could damage your child's lungs.
Drooling and saliva
Medications used to reduce the production of saliva and control the symptoms of drooling are:
hyoscine skin patches – originally designed to treat motion sickness, these patches have the useful side effect of causing a dry mouth
trihexyphenidyl or glycopyrrolate – medicine that causes a dry mouth
Feeding and swallowing difficulties
Feeding young babies with initial symptoms of Tay-Sachs disease can be difficult, because they often lack a suck reflex. This means they have problems latching on to a nipple or the teat of a bottle.
There are a number of things you can do to help, such as helping your baby close their lips around the nipple or teat, or stroking their cheek towards their lips to encourage their suck reflex.
For more information and advice about feeding, you can download a home care manual produced by the support group National Tay-Sachs and Associated Diseases (NTSAD).
Several specialist bottles are available to make feeding easier. They're designed for children with a cleft lip or palate, but are also useful for babies with Tay-Sachs disease. See the Cleft Lip and Palate Association (CLAPA) website for more information.
As your child gets older and moves onto solid food, they may require a feeding tube. There are two main types of feeding tube:
a tube passed down the nose and into the stomach (nasogastric tube)
a tube that's surgically implanted directly into the stomach (percutaneous endoscopic gastrostomy, or PEG tube)
PEG tubes are often recommended for children with Tay-Sachs disease because they're designed for long-term use, but a general anaesthetic is required to fit them.
Medication such as gabapentin and lamotrigine can be useful in preventing seizures, but this can become more difficult as the condition progresses and higher doses may be required.
Problems with muscles, such as stiffness and cramping, can be relieved using medications designed to relax the muscles (muscle relaxants), such as diazepam.
As your child gets older, it's highly likely that they will experience repeated lung infections, which will damage their lungs and prevent them from breathing. This is known as respiratory arrest.
Respiratory arrest can be treated, but often with a low chance of success. In such circumstances, you and your partner may decide that you don't want your child to be treated and that you'd prefer them to die peacefully in their sleep.
If this is the case, you'll need to make what is known as a "do not attempt resuscitation (DNAR) order". Once the order is made, it will be placed with your child's medical records. However, it can be withdrawn at any time should you change your mind. This is a very difficult decision and there's no right or wrong choice.
Some parents decide that even if treatment prolongs their child's life by just a few days or months, it's still precious time they get to spend with their child.
Other parents feel that attempting to resuscitate their child will just prolong the inevitable and that treatment should be withdrawn. Discuss the issue carefully with your partner, family and loved ones.
Research into treatments
Research is being carried out into potential treatments for Tay-Sachs disease.
For example, some researchers are looking into a treatment called gene therapy, which aims to correct the abnormal gene that causes the condition.
However, most of this research is still at an early stage and large studies in humans haven't yet been carried out.
Tay Sachs disease