Ataxia Telangiectasia - Diagnosis

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, IgG subclasses, and IgE) 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.