- What is Ataxia-Telangiectasia?
- How does A-T show itself?
- How is A-T Inherited?
- Is there a cure?
- How rare is A-T?
- What is significant about A-T research?
What is ATAXIA-TELANGIECTASIA? (Called A-T for short)
A-T is a rare, genetic neurological disorder which first shows itself in children at the toddler stage, although it is present at birth. It progressively destroys part of the cerebellum (the motor control area of the brain), leading to lack of balance and inco-ordination. A-T also weakens the immune system, as well as greatly increasing the risk of leukaemia and lymphoma in its young victims.
How is it pronounced? And why is it called Ataxia-Telangiectasia?
Ay-tak-see-a Tel-an-jee-ek-tay-zee-a
This seemingly unpronounceable condition derives its name from the two most obvious clinical features associated with it: "ATAXIA" which is the medical term for unsteadiness and inco-ordination; and "TELANGIECTASIA" meaning web-like dilated blood vessels. These occur in the whites of the eyes, giving them a blood-shot appearance. They appear in the first decade of life of people with A-T.
How does A-T show itself?
Most children with A-T seem normal up until the age that they walk. It is usual for toddlers to be unsteady in their first stages of walking, but with A-T this unsteadiness and inco-ordination gets progressively worse until sufferers eventually become unable to walk unaided and need to use a wheelchair. Speech becomes slurred and laboured, and they develop problems with co-ordinating eye movements. Progressive inco-ordination, due to cerebellar degeneration, means that most people with A-T become unable to perform such simple tasks as feeding and drinking unaided, as well as many other simple manual tasks that most of us take for granted. Frequent respiratory infections are a problem in a proportion of the children due to a deficiency in their immune system. Signs of premature ageing, such as grey hairs, are also associated with A-T.
People with A-T have an increased sensitivity to ionising radiation - the type found in X-rays. Unfortunately, as radiation is one of the main therapies used to treat cancer, great care must be taken when treating someone with A-T.
What is causing the many symptoms of A-T?
In 1995 researchers in Tel Aviv identified the gene responsible for A-T. This was given the name ATM (for A-T Mutated). The ATM protein (product) is believed to play a crucial role in regulating the cell cycle, and in preventing damaged DNA from being reproduced. The cells of people with A-T lack the ATM protein, although the cells of those with the mild form of A-T do contain very small amounts of it. It is thought that ATM is involved in sending messages to several other regulating proteins. Its absence severely disrupts the transmission of these messages, thereby affecting many different systems of the body.
How is A-T inherited?
A-T is caused by recessive genes. This means that an A-T child has inherited one copy of the affected gene from each parent. All of us carry many abnormal genes, but we will usually have a normal matching gene to compensate. It is only if we have a child with someone who also carries the same faulty gene that the child may acquire two copies of the faulty gene (one from each parent). This means there will be no normal gene to compensate for the fault and the child will inherit a genetic disorder. When both parents carry the faulty A-T gene, there is a 1 in 4 chance in every pregnancy of them having an affected child. The ATM gene is located on the long arm of chromosome 11 (11q22-23).
Sadly not at present. Now that the gene has been found we hope that a cure could be more than just a dream. There are now many laboratories around the world analysing the ATM gene product and its effect on cell processes. This is the next important stage towards developing therapies for A-T.
Although it is very rare, A-T is found in every population world wide, with an estimated frequency of between 1/40,000 and 1/100,000 live births. It is currently estimated that there are about 200 cases in the UK, but it is believed that at least 1 in every 100 of the population carries a copy of the faulty (mutated) A-T gene. This could well be significant, as researchers now believe that these gene carriers may also have an increased sensitivity to ionising radiation and that they stand an increased risk of developing cancer - in particular breast cancer in female carriers.
We are also concerned that A-T cases are going undiagnosed and one of the aims of our publicity is to address this problem.
Discovering what is going wrong in A-T will also produce breakthroughs in understanding the causes of cancer, neurodegeneration, immune deficiencies and the process of ageing. This understanding will provide information that will aid research into many other serious conditions that affect all of mankind.
How Recessive Genetic Disorders Are Inherited