What is AT?

     What is AT?

     AT stands for Ataxia-telangiectasia (also know as Louis-Bar Syndrome), a rare disease that affects the nervous system, immune system and other body systems.  The disorder is characterised as a progressive degenerative disease that results in a loss of fine motor skills and often a weakening of the immune system, which results in patients being more susceptible to contracting other illnesses (puts patients at a higher risk).  AT is a disease that occurs in one of every 40,000 to 100,000 people worldwide.

Origin of the Word

Ataxia

     Ataxia describes a lack of muscle control during voluntary movements, such as walking or picking up objects. A sign of an underlying condition, ataxia can affect movement, speech, eye movement and swallowing

Telangiectasia(s)

     Telangiectasias, also known as spider veins or angioectasias, are small dilated blood vessels near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter

Causes

ATM gene loci

     AT is caused due to mutation of the ATM (ataxia-telangiectasia mutated) gene which is located on the long arm of chromosome 11 (11q22.3).  Even though the genetic differences are unfathomably small, the effects have devastating results due to the crucial functions the ATM gene perform within the human body.  The ATM gene is responsible for providing instructions for the making of proteins that help control cell division and is involved in DNA repair.  These proteins assist cells in recognizing damaged or broken DNA strands and help facilitate DNA repair by activating certain enzymes that help to fix these strands.  This is a crucial function required in order to maintain and protect the cell's genetic information.  In AT patients, this gene has undergone mutation during infancy, inhibiting the necessary functions of the ATM gene.  Without the caring out of these functions, cells become unstable and die.  The loss of these cells result in the different side-effects associated with the disease depending on what part of the body where these cells are affected.  In essence, abnormalities occur in chromosome 11 but are not observable, but the resultant is breakage in other chromosomes (can be any) but the most common occurrences are to see breakages in chromosomes 7 and 14.

      

AT patient karyotype

 Inheritance
    

Figure 2-Punnett Square

     AT is a disease that is inherited as an autosomal recessive trait.  This means that it is expressed only when an individual receives the same abnormal gene from both the mother and the father.  However, only one genetically mutated gene is necessary in order to become a carrier of the disease (someone would has genetic differences but do not show symptoms).  As couples who have only one carrier between them cannot produce children in which the disease will be expressed (and therefore are not documented) and those who have already have the disorder only live to their early twenties in most cases (not likely to have children) the most common cases in which children contract AT during infancy is between two heterozygous parents.  The risk for two carrier parents passing on their defective gene and

                                           

Figure 1-Visual Representation

have a child in which the disease is expressed is 25% (RR as illustrated in figure 2) and the likelihood that they receive normal genes from both parents and consequently be unaffected is equivalent (rr as illustrated in figure 2).  Conversely, the likelihood in having a child who is also a carrier (heterozygous) is 50% (Rr as illustrated in figure 2).  AT is a disease that usually begins during infancy (1-3 years of age) and is a disease that often is not isolated to one child (often affects more than one child in a family).  AT affects both sexes equally on average and as previously stated is extremely rare occurring only once every 40,000 to 100,000 births globally (0.001-0.0025%).

Physical Traits and Symptoms
   
     As AT is a disease that affects so many different systems within the human body, the symptoms are astronomical, however, the main affects that can be observed include:

• Ataxia (difficulty with control of movement) that is apparent early but worsens in school to pre-teen years
• Oculomotor apraxia (difficulty with coordination of head and eye movement when shifting gaze from one place to the next)
• Involuntary movements
• Telangiectasia (dilated blood vessels) over the white (sclera) of the eyes, making them appear bloodshot. These are not apparent in infancy and may first appear at age 5–8 years. Telangiectasia may also appear on sun-exposed areas of skin.
• Problems with infections, especially of the ears, sinuses and lungs
• Increased incidence of cancer (primarily, but not exclusively, lymphomas and leukemias)
• Delayed onset or incomplete pubertal development, and very early menopause
• Slowed rate of growth (weight and/or height)
• Drooling particularly in young children when they are tired or concentrating on activities
• Dysarthria (slurred, slow, or distorted speech sounds)
• Diabetes in adolescence or later
• Premature changes in hair and skin (graying of hair for instance)
• Hypersensitivity to ionizing radiation with increased susceptibility to cancer (usually leukemia or lymphoma)
• Endocrine abnormalities including insulin-resistant diabetes mellitus and premature ovarian failure (i.e., normal menarche followed by irregular menses and loss of ovarian function before age 40 years)
• Shortened life expectancy (around 25 years)