Ataxia–telangiectasia
In late pre-school and early school age, they develop difficulty moving their eyes in a natural manner from one place to the next (oculomotor apraxia).
They occur in the bladder as a late complication of chemotherapy with cyclophosphamide,[14] have been seen deep inside the brain of older people with A–T,[15] and occasionally arise in the liver and lungs.
Some people with A–T need additional immunizations (especially with pneumonia and influenza vaccines), antibiotics to provide protection (prophylaxis) from infections, and/or infusions of immunoglobulins (gamma globulin).
[18] Women who are A–T carriers (who have one mutated copy of the ATM gene), have approximately a two-fold increased risk for the development of breast cancer compared to the general population.
Bracing or surgical correction sometimes improves stability at the ankle sufficient to enable an individual to walk with support, or bear weight during assisted standing transfers from one seat to another.
This happens because insertions of retroelements, especially Alu elements, near an exon-intron boundary, cause changes in the splicing sites, resulting in the exclusion of an exon from the mature mRNA.
[citation needed] Therefore, X-ray exposure should be limited to times when it is medically necessary, as exposing an A–T patient to ionizing radiation can damage cells in such a way that the body cannot repair them.
Because programmed DSBs are generated to initiate genetic recombinations involved in the production of sperm and eggs in reproductive organs (a process known as meiosis), meiotic defects and arrest can occur when ATM is not present.
In addition, broken pieces of DNA in chromosomes involved in the above-mentioned rearrangements have a tendency to recombine with other genes (translocation), making the cells prone to the development of cancer (lymphoma and leukemia).
[citation needed] Cells from people with A–T demonstrate genomic instability, slow growth and premature senescence in culture, shortened telomeres and an ongoing, low-level stress response.
[citation needed] A variety of laboratory abnormalities occur in most people with A–T, allowing for a tentative diagnosis to be made in the presence of typical clinical features.
[citation needed] Cerebral palsy (CP) describes a non-progressive disorder of motor function stemming from malformation or early damage to the brain.
CP can manifest in many ways, given the different manner in which the brain can be damaged; in common to all forms is the emergence of signs and symptoms of impairment as the child develops.
Most often the ataxia appears between 10 and 15 years of age, and differs from A–T by the absence of telangiectasia and oculomotor apraxia, a normal alpha fetoprotein, and the frequent presence of scoliosis, absent tendon reflexes, and abnormal features on the EKG.
Those rare individuals with ATLD who are well described differ from those with A–T by the absence of telangiectasia, normal immunoglobulin levels, a later onset, and a slower progression of the symptoms.
Children with NBS have significant microcephaly, a distinct facial appearance, short stature, and moderate cognitive impairment, but do not experience any neurologic deterioration over time.
Like those with A–T, children with NBS have enhanced sensitivity to radiation, disposition to lymphoma and leukemia, and some laboratory measures of impaired immune function, but do not have ocular telangiectasia or an elevated level of AFP.
[citation needed] All individuals with A–T should have at least one comprehensive immunologic evaluation that measures the number and type of lymphocytes in the blood (T-lymphocytes and B-lymphocytes), the levels of serum immunoglobulins (IgG, IgA, and IgM) and antibody responses to T-dependent (e.g., tetanus, Hemophilus influenzae b) and T-independent (23-valent pneumococcal polysaccharide) vaccines.
If the vaccines do not work and the patient continues to have problems with infections, gamma globulin therapy (IV or subcutaneous infusions of antibodies collected from normal individuals) may be of benefit.
[citation needed] If an individual patient's susceptibility to infection increases, it is important to reassess immune function in case deterioration has occurred and a new therapy is indicated.
[citation needed] If the tests show significant abnormalities of the immune system, a specialist in immunodeficiency or infectious diseases will be able to discuss various treatment options.
Absence of immunoglobulin or antibody responses to vaccine can be treated with replacement gamma globulin infusions, or can be managed with prophylactic antibiotics and minimized exposure to infection.
In addition, several "special" vaccines (that is, licensed but not routine for otherwise healthy children and young adults) should be given to decrease the risk that an A–T patient will develop lung infections.
[citation needed] Clearance of bronchial secretions is essential for good pulmonary health and can help limit injury from acute and chronic lung infections.
In people who have decreased lung reserve and a weak cough, use of an insufflator-exsufflator (cough-assist) device may be useful as a maintenance therapy or during acute respiratory illnesses to help remove bronchial secretions from the upper airways.
Evaluation by a Pulmonologist and a CT scan of the chest should be considered in individuals with symptoms of interstitial lung disease or to rule other non-infectious pulmonary processes.
It is important to recognize that intellectual disability is not regularly a part of the clinical picture of A–T although school performance may be suboptimal because of the many difficulties in reading, writing, and speech.
The enhanced effort needed to maintain appearances and increased energy expended in abnormal tone and extra movements all contribute to physical and mental fatigue.
[74] N-Acetyl-Leucine is an orally administered, modified amino acid that is being developed as a novel treatment for multiple rare and common neurological disorders by IntraBio Inc (Oxford, United Kingdom).
[4][6] An open-label Phase II clinical trial studying the use of red blood cells (erythrocytes) loaded with dexamethasone sodium phosphate found that this treatment improved symptoms and appeared to be well tolerated.
