Ataxia Telangiectasia

How many people are affected by this disease?

The ataxia telangiectasia affects about one child per 100,000 with extremes of 1 per 40,000 to 1 per 300,000 according to the publications.

When do the first symptoms occur?

The disease usually starts in children around 1 to 2 years old. It affects childeren from both sexes regardless of their geographical origin.

What is AT and what is its origin?

Ataxia telangiectasia (AT), also known as Louis-Bar syndrome, is a rare, neurodegenerative and immunosuppressive disorder. It is an inherited disease that affects many parts of the body and causes serious disabilities. Ataxia is defined by a lack of coordination of movements and telangiectasia are visible blood vessels especially in the whites of the eyes.

The gene responsible for this disease is called the ATM gene and is located on chromosome 11. Its structure has only been known since 1995. More than 1000 different abnormalities (ie mutations) are known for this gene, which makes the research for possible treatment rather difficult as these mutations can occur in all regions of the gene; there is no particular location.
We can also notice some mutations more present in certain populations which sometimes makes it possible to orient research according to the geographical origin of the patient. Most of these mutations lead to an absence of production of the ATM protein and because of this, it does not exist in the patient.
However, it intervenes in the control of the repair of the breaks occurring on the DNA, support of the genetic information.
The absence of protein in sick children therefore prevents cell cycle arrest in the event of DNA damage and therefore leads to the persistence of chromosomal breaks and an excess of cell death that causes early aging.

What are the signs and symptoms of the disease?

The manifestations of ataxia telangiectasia are very variable.
The disease affects the nervous system, the skin and the immune system, which results in a higher risk of infections and cancers.

First, the involvement of the nervous system is linked to cerebellar involvement (cerebellar ataxia) .The cerebellum is an organ located in the cranial box, below the cerebral hemispheres.
it is vital for the balance and coordination of movements.
Balance disorders are one of the first manifestations. They gradually appear when the child has normal walking and is associated with abnormal movements of the head. These disorders progress slowly, between the age of 2 and 4 years the motor progress of the child with increase of his address tend to hide the progression of ataxia. After the age of 5, the progression of ataxia becomes visible again and children often need a wheelchair around the age of 10 to 11, even if they maintain good muscular strength. The evolution of ataxia, however, varies from one child to another, including children affected in the same family. Disturbances in pronunciation and eye movements occur quite early.
The poor coordination of movements and the tremor of the extremities appear gradually in some children, from the age of 9-10 years and cause discomfort to write. Large abnormal movements (choreoathetosis) are quite common.
All of these disorders progressively worsen, and adolescents often need help getting dressed, eating and washing. In most cases, intelligence is normal although motor and speech disorders interfere with patients in IQ tests. Many patients are studying. However, about 30% of patients have learning disabilities or moderate intellectual disability.

Also, the cutaneous signs are manifested by the dilation of the small peripheral vessels (telangiectasias) which are one of the common manifestations of the disease after the neurological manifestations. These telangiectasias appear a little later than the neurological signs, around the age of 3 to 6, sometimes even in adolescence.
In the beginning, they are located at the level of the “white of the eye” on the conjunctiva, then, inside the ears, on the eyelids and at the level of the folds of the elbow and the knees.
Some signs of premature aging may be visible in the hair and skin: grey hair, thinned skin (atrophic), less soft ears…

Then, we can also talk about the deficiency of immunity being at the origin of pulmonary infections or sinusitis with repetition. Repeated pulmonary infections can in the long run damage the lungs and cause bronchial dilatation (bronchiectasis).

We can notice a relative increase in the frequency of cancers compared to the general population.
The risk for patients to develop cancer is estimated between 10 to 35%
In children, it is primarily acute lymphoblastic leukemia and lymphoma whereas in adults, it is rather solid tumors (cancer of the thyroid, breast …).

To end with the manifestations of the disease, we notice a stunting quite common.

How to make a diagnosis?

The clinical diagnosis of ataxia telangiectasia is based on various manifestations such as gait disorders, abnormal eye movements, conjunctival telangiectasias and repeated pulmonary infections. However, making a diagnosis can be difficult because not all of these symptoms are always present in young children, which may occur later.
This is why complementary tests (MRI, DNA and blood tests) are performed. The blood level of alphafoetoprotein (a variety of protein manufactured, normally only during fetal life) is high in the majority of patients.
There is also a deficiency in several types of immunoglobulins (IgG2, IgG4, IgA and IgE). The blood karyotype (examination of chromosomes from a blood test) shows, in 5 to 10% of T lymphocytes, various chromosomal rearrangements concerning chromosomes 7 and 14. Finally, the analysis of the gene confirms the diagnosis with certainty if two mutations are found. However, gene analysis is difficult and this confirmation is not always possible.

How is the disease transmitted?

Ataxia telangiectasia is transmitted in an autosomal recessive fashion. This means that only children who have received the mutated gene from both their father and mother are affected. Thus, the affected people carry the mutated gene in two copies (they are called homozygotes) while each of the parents is carrying only one copy (they are called heterozygotes). This disease usually affects only siblings of the same family. The probability of having another child is 1 in 4 for a couple who have already given birth to a sick child.

What are the existing treatments?

To date, there is treatment to cure for AT. There are things that can improve the patient’s daily life such as: physiotherapy, speech therapy, occupational therapy. Rehabilitation is essential, it helps to delay the progression of disability at all levels: walking, speaking, reading, writing, swallowing, …

However, medical research is underway in countries like USA, Israel or the Netherlands, Holland,… So we must continue to hope that a treatment will become available soon..