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Ataxia Telangiectasia

Ataxia Telangiectasia


Ataxia Telangiectasia (AT) is a rare genetic disease that affects the nervous system, the immune system, and other body systems. This disease is characterized by difficulty in coordinated sexual movement (ataxia) that begins in early childhood, usually before 5 years of age. And neurological dysfunction (neuropathy). Movement problems often cause people to need wheelchair assistance during adolescence. People with this disease also have difficulty speaking and have difficulty moving their eyes to the side (oculomotor apraxia). Small clusters of dilated blood vessels called telangiectasias that appear on the surface of the eyes and skin are also characteristic of this condition.

Ataxia Telangiectasia

 The blood of affected people often contains a large amount of a protein called alpha-fetoprotein (AFP). The level of this protein generally increases in the blood of pregnant women, but I don’t know why people with ataxia vasodilators have elevated AFP, or what effect it has on these people.

 People with ataxia vasodilators often have a weakened immune system, and many people develop chronic lung infections. They are also at increased risk of cancer, especially hematopoietic leukemia and lymphoma of the immune system. Affected people are very sensitive to the effects of radiation exposure, including medical X-rays. The life expectancy of patients with ataxia vasodilators varies widely, but affected individuals often live into early adulthood.

 Vasodilators of ataxia are inherited in an autosomal recessive manner, which means that there are mutations in both copies of the ATM gene in every cell. In most cases, the parents of an individual with an autosomal recessive genetic disease each carry one copy of the mutated gene, but do not show the signs and symptoms of the disease.

 Among people with AT, progressive ataxia usually occurs in childhood and may initially be characterized by abnormal head and trunk oscillations. As the disease progresses, this condition can make it impossible to walk (wander) in late childhood or adolescence. Ataxia is often accompanied by slurred speech (dysarthria), drooling; poor coordination of certain eye movements (eye movement apraxia), including attempts to focus on certain objects (gaze Nystagmus) is the rapid, involuntary, rhythmic movement (oscillation) of the eye. Affected children may also have abnormal hunchback postures and jerky, fast and irregular movements, which may be related to relatively slow torsional movements (dance athetopathia). In addition, telangiectasias can develop in mid-childhood and usually appear in areas of the skin exposed to the sun, such as the bridge of the nose, ears and certain areas of the limbs, and the mucous membranes of the eyes (conjunctiva).

Ataxia Telangiectasia

 Ataxia telangiectasias It is caused by a mutation in the ATM gene and is located on chromosome 11q2223. Mutations in the ATM gene are responsible for abnormal repair of double-stranded DNA breaks. Due to this defect, the response of the cell to different pathogenic factors (such as ionizing radiation and alkylating agents) is affected. As a result, cell death occurred in susceptible tissues such as the cerebellum and malignant proliferation occurred.

 About 1% of the US population carries one mutant copy and one normal copy of the ATM gene in each cell. These people are called carriers. Although carriers of the ATM mutation do not have ataxia vasodilators, they are more likely to develop cancer than people without ATM mutations; Carriers are at particularly high risk for breast cancer. Carriers of ATM gene mutations may also increase the risk of heart disease. The incidence of

 AT is 1:40,000 to 1:100,000. In some populations, the rare rate of this disease is 1:300,000. In the United States, approximately 1% of the population carries mutations in the ATM gene. Men and women are also affected by AT. Ataxia telangiectasia is the second most common autosomal recessive ataxia in children, second only to Friedreich ataxia, but it is the most common hereditary ataxia starting with the first ten years. According to reports, among different groups of people, especially in North African Jewish communities, there is a significant founder effect.

 A mutation in the ATM gene is the cause of AT. Nonsense, frameshift, nonsense and indel mutations of ATM genes have been described as related to AT. In most cases, mutations will cause the protein to be truncated and therefore lose function. Compound heterozygous mutations are also rare.

 ATM involves many different molecular mechanisms. This protein is most important for cellular DNA repair, cell cycle control, and cellular response to external triggers such as oxidative damage, ionizing radiation, and alkylating agents. The protein itself is a serine / threonine kinase that affects many different downstream targets, which are involved in pathways that are important for cellular protection from toxicity. Therefore, due to unrepaired double-stranded DNA breaks, loss of ATM protein function is the cause of abnormal cell proliferation, increasing cancer risk and radiosensitivity. In addition, disorders of cell cycle control can lead to malformations, such as hypogonadism, which is found in patients with Ataxia Telangiectasia. Furthermore, ATM is also important for immunoglobulin production and lymphocyte survival. This explains why ATM mutations cause an increased risk of tumors of the lymphatic system and autoimmune manifestations.

 The underlying mechanism of telangiectasia is still unknown. This condition can cause the blood vessels to dilate, which is one of the hallmarks of this disease. Ataxia Telangiectasia autopsy cases mainly report degeneration of the cerebellar cortex. Purkinje cells and granule cells are particularly affected. As the disease progresses, other parts of the brain will gradually degenerate, especially the brain stem, posterior and anterior horns of the spinal cord.

Telangiectasia is another hallmark of the disease, which is present in almost all cases. They usually become obvious after 6 years of age. Capillary dilation most often occurs in the eyes, especially the conjunctiva and/or areas exposed to sunlight (such as the face and ears). They can also be found in the brain and bladder.

About 25% to 30% of AT patients will develop tumors. Leukemia and lymphoma are more common early in life. Later solid tumors such as breast and ovarian cancer, melanoma, stomach cancer or liver tumors can appear. Tumors can also be related to severe radiosensitivity. In particular, X-rays and gamma rays are reported to be harmful to AT patients, with the exception of ultraviolet (UV) rays, so they should be avoided.


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