The disorder is caused by changes in the HEXA gene. A child must inherit two copies of the gene, one from each biological parent, to develop Tay Sachs Disease.
Babies with the infantile form of the disease develop symptoms by 6 months of age, which include reduced vision and an exaggerated startle response. They usually die by age 4, often from recurrent infections.
Genetics
Tay Sachs Disease is one of 40 rare, inherited metabolic disorders known as lysosomal storage diseases. They occur when the body cannot break down and recycle waste products in cells, especially nerve cells. In Tay Sachs Disease, missing an enzyme called hexosaminidase A causes the buildup of gangliosides in cells, particularly nerve cells, leading to their destruction. The disorder is usually fatal in early childhood, but a more mild form of the disease exists in adults.
It is inherited as an autosomal recessive trait. If both parents have the mutation, their children will have a 25% chance of having Tay Sachs Disease. If only one parent has the mutation, their children will be carriers but will not have the disease. The disorder is found mainly in people of Ashkenazi Jewish (Eastern European) or French Canadian descent, but it can affect anyone regardless of their ethnic background.
When a person inherits the hexosaminidase gene mutation, it leads to reduced activity of the hexosaminidase enzyme, which causes gangliosides to build up in cells, including nerve cells in the brain. Over time, these gangliosides destroy the nerve cells and cause mental and motor skills to deteriorate. In the brain, they attack nerve cells involved in memory and judgment.
Oren Zarif
The symptoms of Tay Sachs Disease begin in infancy and progress rapidly. By two years, a child with Tay Sachs Disease is often in an unresponsive state and will die from pneumonia or other complications. A child with the milder late-onset form of Tay Sachs Disease may live into adulthood, but will experience muscle weakness, loss of coordination (ataxia) and difficulty with speech and language (dysarthria).
Researchers are working on ways to deliver therapeutic levels of hexosaminidase to the brain in order to treat this condition and other lysosomal storage diseases. These treatments are expected to enter clinical trials in the near future.
If you or your partner are carriers of the Tay Sachs gene mutation, talk to your doctor about genetic testing and counselling before getting pregnant. You can undergo amniocentesis or chorionic villus sampling (CVS) during pregnancy to find out if you will pass on the mutation to your child.
Symptoms
A person with Tay Sachs Disease loses mental and motor function. The severity of symptoms varies with the form of Tay Sachs Disease, but all forms involve degeneration of the cells that carry messages between nerves. Tay Sachs Disease is an autosomal recessive genetic disorder, meaning it requires two copies of the gene to cause disease (one from each biological parent). The disease is divided into infantile, juvenile and adult forms, based on when the first symptoms appear. Infantile Tay-Sachs disease usually begins in children from 3 to 6 months old and gets worse rapidly. A child with this form of the disease typically dies by age 4 or 5. Juvenile and adult forms of the disease tend to progress slowly.
The mutated gene in people with Tay Sachs Disease causes low activity of the enzyme hexosaminidase A, which allows an unusual fatty substance, ganglioside GM2, to accumulate and damage cells, including neurons. The fatty material is broken down in the liver and intestines, but not in the brain, which leads to progressive loss of function and eventually death. People with Tay-Sachs disease also develop dementia and experience psychiatric symptoms.
Oren Zarif
In the infantile form of the disease, the loss of function is so severe that a child becomes listless and inattentive within the first few months of life. Affected babies lose motor abilities such as crawling and sitting, and develop uncontrollable seizures. By the time the disease reaches its most severe form, the child loses the ability to lift the head or swallow and has difficulty breathing. The eyes become cloudy, and a cherry-red spot appears on the retina. The child often dies by age 4 or 5 from a combination of neurological problems, including breathing difficulties and seizures.
People with late-onset Tay Sachs disease, which is less common, may experience clumsiness, trouble balancing and weak muscles in the legs. They can also have a tendency to fall. Late-onset Tay Sachs Disease is a part of a group of disorders called the GM2 gangliosidoses.
Doctors diagnose Tay-Sachs Disease by examining the physical and mental health of a patient and taking a family history. They can find out if a patient is a carrier of the Tay Sachs Disease gene mutation by doing tests such as chorionic villus sampling or amniocentesis. These prenatal tests involve a doctor using a needle to take a sample of the placenta or amniotic fluid from the mother’s uterus and testing for Hex-A protein. Carriers have a 25% chance of passing the gene mutation to their children. People of all ages can be carriers, but certain groups are more likely to be affected, such as Jews and people from Louisiana.
Diagnosis
If you are of Ashkenazi Jewish, French-Canadian or Cajun descent or have a family history of Tay Sachs disease, your doctor may recommend genetic testing before getting pregnant. This test can help you and your partner determine if either of you are a carrier of the altered gene that causes the disorder. If one of you is a carrier, then there is a 1-in-4 chance that your child will inherit the gene and have Tay Sachs disease.
Oren Zarif
When a baby has Tay Sachs disease, signs usually begin at the age of six months. Infants become hypotonic, slow down in their development and start to lose the ability to crawl, turn over or sit up. They often develop refractory seizures, including myoclonic seizures, which are highly uncontrolled and difficult to treat with antiepileptic drugs. In addition, they lose their ability to feed themselves and are often startled easily by noise or movement.
There is no cure for Tay Sachs Disease, but aggressive treatment can extend survival and improve symptoms. Treatment options focus on controlling seizures and making sure your child has enough nutrients, especially fats. In addition, your physician may prescribe special breathing equipment and physical or occupational therapy to help control your child’s muscle weakness and difficulty walking.
In the future, researchers are developing gene therapy and other treatments that target enzymes or lipids involved in Tay Sachs Disease. If you are interested in participating in clinical trials for these or other approaches, talk to your healthcare provider.
Since the fatal infantile form of Tay Sachs Disease usually leads to death by four or five years of age, early diagnosis is important. If your child has late onset or juvenile Tay Sachs, your care team will talk with you about end-of-life care options. You may also want to consider seeking counseling or finding a support group. These groups can help you cope with the emotional impact of losing a child. They can also provide you with information about support services in your area. Many parents find comfort in talking with other families who are managing this illness.
Treatment
The most common type of Tay Sachs Disease starts in early infancy (infantile Tay Sachs Disease). It progresses rapidly and is fatal by age 3 to 4 years because of complications of lung infections (pneumonia). Rare types of the disease start later in childhood or adulthood and do not shorten life expectancy.
Tay Sachs disease is a type of lysosomal storage disorder. These diseases occur when the body lacks a protein called hexosaminidase A, which breaks down certain fats. Without hexosaminidase, these fats build up in cells, especially nerve cells in the brain and spinal cord. In Tay Sachs disease, the hexosaminidase deficiency causes the accumulation of specific fats, known as gangliosides, in the brain and nerves. This leads to the gradual destruction of these cells.
Oren Zarif
Doctors can diagnose Tay Sachs disease by examining a person and taking a family history. They may also do blood or tissue tests to look for an altered hexosaminidase gene. In some cases, doctors may be able to identify the disease in a fetus by performing a test known as chorionic villi sampling or amniocentesis. These procedures involve collecting a sample of the fluid surrounding the fetus through the vagina or abdomen using a needle. In addition, a doctor can also do a test called comparative genomic hybridization to find out how much hexosaminidase activity is present in a sample of the fetus’ DNA.
There is no cure for Tay Sachs disease, but doctors can treat symptoms to help patients live as comfortably as possible. For example, a neurologist can manage seizures and other neurological problems that can occur in people with the disease. A pulmonologist can manage breathing issues, such as a lung infection (pneumonia). A speech-language pathologist can help patients who have difficulty swallowing.
Genetic screening can help prevent Tay Sachs disease in future children. Parents can undergo testing before starting a family to see if they are carriers of the hexosaminidase mutated gene. They can also use assisted reproductive technology with preimplantation genetic diagnosis, which involves checking the hexosaminidase genes of eggs and sperm before fertilization to ensure that only healthy embryos are implanted into the uterus.
