Defects in neuronal function: Inappropriate cell cycle re-entry of post-mitotic (mature) neurons Synaptic/vesicular dysregulation HDAC4 dysregulation Histone hypermethylation and altered epigenetics Altered protein turnover These hypotheses may not be mutually exclusive and more than one of these mechanisms may underlie neuronal cell death when there is an absence or deficiency of ATM. Further, cerebellar damage and loss of Purkinje and granule cells do not explain all of the neurologic abnormalities seen in people with A–T. The effects of ATM deficiency on the other areas of the brain outside of the cerebellum are being actively investigated. Radiation exposure People with A–T have an increased sensitivity to ionizing radiation (X-rays and gamma rays). 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. The cells can cope normally with other forms of radiation, such as ultraviolet light, so there is no need for special precautions from sunlight exposure. Diagnosis 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). 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. Not all abnormalities are seen in all patients. These abnormalities include: Elevated and slowly increasing alpha-fetoprotein levels in serum after 2 years of age Immunodeficiency with low levels of immunoglobulins (especially IgA, IgM, IgG, and IgG subclasses) and low number of lymphocytes in the blood Chromosomal instability (broken pieces of chromosomes) Increased sensitivity of cells to x-ray exposure (cells die or develop even more breaks and other damage to chromosomes) Cerebellar atrophy on MRI scan The diagnosis can be confirmed in the laboratory by finding an absence or deficiency of the ATM protein in cultured blood cells, an absence or deficiency of ATM function (kinase assay), or mutations in both copies of the cell's ATM gene. These more specialized tests are not always needed, but are particularly helpful if a child's symptoms are atypical.