Abstract Ataxia-telangiectasia is an inherited disease related to an autosomal recessive trait. This means that both parents must provide a defective gene for the child to have symptoms of the disorder. The disease results from defects in the ataxia telangiectasia mutated (ATM) gene. Defects in this gene can lead to abnormal cell death in various places of the body, including the part of the brain that helps coordinate movement. During development boys and girls are equally affected.
Symptoms can include obvious gross decreased coordination of movements in late childhood to include delayed eye hand coordination, uncoordinated or jerky gait which comes from cerebellar ataxia, decreasing mental development, discoloration of skin areas, enlarged blood vessels in the skin of nose, ears, and inside of the elbow and knee, enlarged blood vessels in the sclera, nystagmus as a late sign, seizures and even severe recurring respiratory infections unfortunately there are not treatments as of yet for this illness and we can only treat the symptoms as they occur and progress.
Life expectancy and prognosis decreases throughout the years but can vary. The only prevention of this illness that is known today is that parents with this known genetic train to abstain from trying to have children with out genetic counseling first. “Ataxia telangiectasia, also refereed to as AT or Louis-Bar Syndrome) is a primary rare, neurodegerative, inherited immunodeficiency disease that affects a number of different organs in the body but primarily the CNS. An immunodeficiency disease is one that causes the immune system to break down, making the body susceptible to diseases.
A rare, recessive genetic disorder of childhood that occurs in between 1 out of 40,000 and 1 out of 100,000 persons worldwide. The disease is generally fatal to patients by the time they reach their twenties and it effects both boys and girls are the same rate”. A-T is characterized by neurological problems, particularly abnormalities of balance, recurrent sinus and respiratory infections, and dilated blood vessels in the eyes and on the surface of the skin. t impairs certain areas of the brain including the cerebellum, causing difficulty with movement and coordination.
Patients usually have immune system abnormalities and are very sensitive to the effects of radiation treatments. In the United States, where recurrent infections typical of the disorder are usually controlled by antibiotics, patients are at high risk of developing and dying of cancer, particularly leukemias and lymphomas due to to depressed immune system and the fact that AT can actually prevent the repair of broken DNA, increasing the risks of above listed cancers.
Symptoms most often first appear in early childhood when children begin to walk and though they usually will start walking at a normal age, their ability to perform this function will appear very problematic. In late pre-school and early school age patients will develop issues with extra ocular motor control. Though they will still be able to focus on objects and see clearly, they will have issues purposely turning their eyes towards an object or sound.
Patients can develop numerous respiratory infections. “A-T is caused by a defect in the ATM gene, which is responsible for managing the cell’s response to multiple forms of stress including double-strand breaks in DNA. In simple terms, the protein produced by the ATM gene recognizes that there is a break in DNA, recruits other proteins to fix the break, and stops the cell from making new DNA until the repair is complete”.
If this ATM gene is not present, ion channels in neurons are degraded and chemical activity is retarded, slowed and even stopped thus creating a lapse in communication between axons and other neurons long that communication pathway to organs and other sensory pathways. Purkinje and granule cells are often affected as well and degeneration of these same cells in the cerebellum has also been detected in autopsy studies of individuals with autism. Affected children also have telangiectases, “spider” veins appearing in the sclera of the eyes or on the skin more exposed to sunlight.
This is usually an early sign that can be linked to the disease and will show up near the age of 6 or 7. “Many affected children with this disorder also have low serum IgA, IgG, IgG-2, IgG-4 and/or IgE. IgG-4 and IgG-2 levels are almost always undetectable or low in every patient and an IgG-3 deficiency can be associated with the IgG-2 and IgG-4 defect in patients with undetectable IgA. IgG-1 can be very low in patients with a total IgG deficiency. ” In a sense, this illness causes not only poor or a total lack of immunoglobulines but a degradation of neurological tissue and neuropathy.
“The diagnosis of A-T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with telangiectasia and sometimes increased infections, and confirmed by specific laboratory abnormalities (elevated alpha-fetoprotein levels, increased chromosomal breakage or cell death of white blood cells after exposure to X-rays, absence of ATM protein in white blood cells, or mutations in each of the person’s ATM genes). ”
“It is increasingly clear that ataxia can result directly from mutations in ion channels or from perturbations in ion channel physiology in the absence of a primary channel defect. Neuronal dysfunction stemming from perturbed channel activity likely explains some motor deficits in episodic and degenerative ataxias”( Paulson ). Physical adaptations of the human body in relation to this illness unfortunately are limited if not all together non-existent. Much like Parkinson, MS and other autoimmune diseases, there are have been few advances in finding cures and we have yet to be able to treat more than the symptoms that present themselves.
As the illness progresses, and the brain and neurological systems fail, the body loses its ability to function properly as there are fewer neural connections and greater degradation within the nervous system. Feeding and drinking can become and issue as the disease progresses with age as well. Feeding oneself requires a good deal of eye hand coordinations and gross and fine motor skills that are all controlled by the cerebral cortex and as those neurons break down, the motor control does as well. Dysphagia can become an issues generally in the 2nd decade of life if the patients lives that long.
Problems with coordination involving the pharynx can cause liquid, food, and saliva to be inhaled into the airway leading to whats known as silent aspiration and some people with dysphagia may not have a gag reflex or a cough reflex and can choke easily on food leading to hypoxia, more neurological damage due to lack of oxygen, coma, a vegetative state, brain damage or even death. The vast majority of individuals develop the T part of AT, which is Telangiectasia, or a grouping of prominent blood vessels found in the sclera, or the white part of the eye.
This generally comes later in the disease after the patient as lost a good deal of their ocular motor control and the body is trying to regain and repair what it can by trying to re-profuse the eyes with new blood vessels. Although oculomotor control decreases, visual acuity generally stays intact as the function of focusing can be a passive action requiring little muscular control of the iris. Eye misalignments might be present but can be treated. Orthopedics takes a huge toll when this disease starts in as one can expect with a loss of motor control.
Many people develop issues with their feet that further increase problems with walking. Bracing or surgical corrections and fixations can sometimes correct issues with the ankles but that is usually a last resort and does not help much. Since the neurological system is in an unfortunate constant path of failure, coordination is lost because of a loss of the cerebral tissue, as is the definition of ataxia. Defects in the ATM gene lead to abnormal and early cell death in various places in the body and the cerebral cortex and cerebellum.
Along with negative physical adaptations, nearly 2/3 of the individuals that develop AT have abnormalities of their immune system. The most common are low levels of immunoglobulins and low levels with T-cells. Given these issues, an individual’s chance of getting sick or catching a communicable disease is greatly increased. Most common are respiratory illnesses and unfortunately cancers. Lymphomas and leukemia are the cancers most commonly found with AT patients as well as lung diseases because of the chronic respiratory infections.
A patient with AT is at a much higher risk of developing cancers not only in the respiratory system but also in the GI tract, the skin, sexual reproductive organs, and hormone producing glands. “A small number of individuals develop interstitial lung disease. They have decreased pulmonary reserve, trouble breathing, a need for supplemental oxygen and chronic cough in the absence of lung infections. They may respond to systemic steroid treatment or other drugs to reduce inflammation” (Crawford). AT can also cause signs of premature aging such as graying of the hair and vitiligo, an autoimmune disease that causes the loss of skin pigment.
Warts can become an issue and even if treated, can reoccur and rapidly reproduce. Some individuals even develop inflammatory skin diseases. Interventions and the prognosis of AT are unfortunately limited as there is not yet a cure and only the symptoms of this disease are treatable. There is not yet a treatment to slow the progression of the neurologic problems and supportive treatment is just about as good as one can hope for until more genetic testing and further gene studies can reveal a treatment or cure.
“ Therapeutic exercises should not be used to the point of fatigue and should not interfere with activities of daily life. Certain anti-Parkinson and anti-epileptic drugs maybe useful in the management of symptoms, but should be prescribed in consultation with a neurologist” (Paulson). With the unfortunate lack of treatment options, as a child progresses through his years, the options for help decrease while the need unfortunately for it increases.
The continued degradation of the CNS and immune system furthers any other illness and lowers and retards any prognosis for other illnesses that the child might incur. In summary, before Ataxia-telangiectasia takes control of a humans body, there are no precursors or signs that the illness is present. Bodily functions are normal and only once symptoms occur is there any notion of testing for this disease unless one or both of the parents are eknown carriers or have the missing ATM gene in their family tree. The main changes in anatomy are destruction of the neurological tissue of the brain.
Ion channels form pores in cell membranes and these channels “play a huge role in regulating neuronal electrical excitability” and with the mutation of these channels or the cells around them, neuron activity is limited, degraded, and even stopped all-together. Other systems are not directly affected but because the CNS is effected the bodily organs are affected second hand by a loss of that specific motor control. There are few chemical changes to the body; mainly physical changes as the disease progresses and the body is unable to support itself in daily functions.
The brain slowly dies and therefor its ability to control the smooth, striated and cardiac muscle tissue degrades. There are no treatments for the illness itself but one can be treated for symptoms. If cancer is being treated it is best to avoid radiation therapy chemotherapy drugs as they can be toxic to these patients. Surgical treatments can include fixation of joints but should be used as a last resort to help with posture and what ambulation the patient might have left.
Prognosis for these patient’s is limited, varies and can change throughout the course of the patient’s life; although life expectancy decreases with every year. Each individual will be affected differently but most will not live past college age and if they do, their quality of life is severely affected in a negative way. Understanding Ataxia-telangiectasia, while not important to every individual , is important to those hoping to start and settle into a career in pediatrics or even oncology.
Understanding illnesses that can affect your children should be a worry of every parent especially if they know their family tree contains at least one autoimmune disease as there are generally more to be found, recessive or not .
References US National Library of Medicine (August 4, 2011) retrieved from http://www. ncbi. nlm. nih. gov/pubmedhealth/PMH0002369/ National Cancer Institute (January 1, 2006) retrieved from: http://www. cancer. gov/cancertopics/factsheet/Risk/ataxia US National Library of Medicine ( June, 2008) retrieved from: http://ghr. nlm. nih. gov/condition/ataxia-telangiectasia Crawford, TO (1998 Dec). “Ataxia telangiectasia. “.
Seminars in pediatric neurology Reiman, A; Srinivasan, V, Barone, G, Last, JI, Wootton, LL, Davies, EG, Verhagen, MM, Willemsen, MA, Weemaes, CM, Byrd, PJ, Izatt, L, Easton, DF, Thompson, DJ, Taylor, AM (2011 Aug 9). “Lymphoid tumors and breast cancer in ataxia telangiectasia; substantial protective effect of residual ATM kinase activity against childhood tumors. “. British journal of cancer 105 (4): 586–91. US National Library of Medicine ( October, 2009 ) “ Physiologic alterations in ataxia: Channeling changes into novel therapies” retrieved from: http://www. ncbi. nlm. nih. gov/pmc/articles/PMC2762109/.