Ataxia Telangiectasia (AT) is a complicated hereditary neurodegenerative condition that can manifest in early childhood or during infancy. The problem is characterized by increasingly disordered voluntary movement coordination (ataxia), the growth of reddish lesions of the skin and mucous membranes because of permanent widening of groups of blood vessels (telangiectasia), and decreased immune system functioning (i.e., cellular and humoral immunodeficiency), all of which lead to increased susceptibility to upper and lower respiratory infections called sinopulmonary infections. Individuals with ataxia telangiectasia are also more likely to acquire some cancers, including those of the lymphatic system (lymphoma), blood-forming organs (e.g., leukemia), and the brain.
Ataxia-telangiectasia is a recessive autosomal condition. Two genes, one from the father and the other from the mother, determine genetic illnesses.
When an individual receives the same faulty gene for the same trait from both parents, they are said to have recessive genetic diseases. If a person is born with one normal gene and one illness gene, he or she will be a carrier for the disease but will not display symptoms. With each pregnancy, there is a 25% chance that two carrier parents will both carry the faulty gene and, as a result, have an afflicted child. With each pregnancy, there is a 50% chance of having a child who is a carrier like the parents. A child has a 25% probability of receiving normal genes from both parents and being genetically normal for that attribute.
The ATM gene, which causes ataxia telangiectasia, is found on the long arm (q) of chromosome 11 and is responsible for the disease (11q22.3). All bodily cells have chromosomes in their nuclei. They include each person’s genetic features. Human chromosomal pairs are numbered 1 through 22, with males having an uneven 23rd pair of X and Y chromosomes and females having two X chromosomes. Each chromosome has a short arm (the letter “p”) and a long arm (the letter “q”). Chromosomes are further separated into bands, each of which is assigned a number.
Researchers discovered that the ATM gene codes for a protein that regulates cell proliferation following DNA damage. (The genetic code is carried by DNA or deoxyribonucleic acid.) The ATM protein, which stands for “ataxia telangiectasia mutated,” is a protein kinase enzyme that ordinarily responds to DNA damage by causing the buildup of a protein called p53, which prevents cells from proliferating (tumor suppressor protein). However, aberrant changes (mutations) in the ATM gene produce a lack or deficiency of the ATM protein and delayed accumulation of the p53 protein in people with ataxia-telangiectasia. As a result, cells with DNA damage continue to divide (replicate) without receiving adequate DNA repair, increasing the risk of cancer formation. Anomalies affecting the activity of the p53 tumor suppressor protein are thought to be present in about half of all human malignancies. Ionizing radiation (such as x-rays) generally increases the ATM protein’s p53-directed activity; but, in people with ataxia-telangiectasia, the ATM protein’s activity is insufficient, resulting in heightened vulnerability to such radiation.
Ataxia telangiectasia can also be caused by mutations in the ATM gene. The ATM gene gives instructions for manufacturing a protein that aids in cell cycle regulation and DNA repair. This protein is essential for the proper development and function of various physiological systems, including the neurological and immunological systems. The ATM protein helps cells recognize damaged or broken DNA strands and organizes DNA repair by activating enzymes that repair the damage. Repairing broken DNA strands effectively contributes to the stability of the cell’s genetic information.
The ATM protein’s function is reduced or eliminated when the ATM gene is mutated. Cells that lack this protein become unstable and perish. The loss of the ATM protein has a particularly negative impact on cells in the cerebellum, which coordinates movements. Some of the mobility issues associated with ataxia-telangiectasia are caused by the death of these brain cells. Mutations in the ATM gene also prevent cells from responding appropriately to DNA damage, allowing breaks in DNA strands to accumulate, which can lead to the development of cancerous tumors.