Diagnosing A-T A Note to Physicians

Possible Symptoms of A-T

  • progressive cerebellar ataxia (although ataxia may appear static between the ages of two and five years)
  • progressive oculocutaneous telangiectases appearing by the age of six years
  • susceptibility to neoplasia
  • characteristic hypotonic facies
  • progressive apraxia of eye movements (slow initiation)
  • absence or dysplasia of thymus gland
  • recurrent sinopulmonary infection
  • choreoathetosis
  • slowed growth
  • cerebellar dysarthria and drooling
  • equable disposition
  • endocrine abnormality
  • proneness to insulin-resistant diabetes in adolescence
  • progeric changes in hair and skin and progeric vascular changes
  • cortical cerebellar degeneration, involving mainly the Purkinje and granule cells

Clinical Variability

Tremendous clinical variability is seen among A-T patients, and therefore, many of these symptoms will not be seen in any one patient.

The Clinical Presentation of A-T

…almost always includes the onset of cerebellar ataxia between the ages of two and five years. Other, less consistent features may include: dysarthria and drooling, oculocutaneous telangiectasia, progressive apraxia of eye movements, characteristic hypotonic facies, absence or dysplasia of the thymus gland, recurrent pulmonary infections, susceptibility to neoplasia, slowed growth, endocrine abnormalities and progeric changes in the hair and skin.

Common Errors in the Diagnosis of A-T . . .

To the physician at the A-T Clinical Center who has seen hundreds of patients with A-T, the diagnosis can usually be made on purely clinical grounds and often on inspection. But, because most physicians have never seen a case of A-T, mistakes are likely to occur.

For example, perhaps because of the disorder’s name, physicians examining ataxic children frequently rule out A-T if telangiectasia are not seen. However, telangiectasia often do not appear until the age of six, and sometimes much older. Similarly, a history of recurrent sinopulmonary infections would heighten suspicion, but about 30 percent of people with A-T do not have immune problems.

The most common early misdiagnosis is that of static encephalopathy (so-called “ataxic cerebral palsy”). Even though truncal and gait ataxia, almost always the presenting symptom in A-T, is slowly and steadily progressive, it may be compensated for by the normal development of motor skills between the ages of 2 and 5 years, which may mask the progression of ataxia so that an impression of improvement is often reported. As a result, until the progression of the disease becomes apparent, clinical diagnosis will often be incorrect and uncertain unless the patient has an affected sibling.

Once the progression of the disease becomes apparent, Friedreich’s ataxia becomes the most common misdiagnosis. However, Friedreich’s ataxia usually has a later onset and the typical pes cavus and kyphoscoliosis are highly characteristic. The spinal signs involving posterior and lateral columns along with the positive Romberg sign distinguish this type of “spinal” ataxia from the primary cerebellar ataxia of A-T.

Possible Markers of A-T

  • elevated serum alphafetoprotein after two years of age
  • elevated plasma carcinoembryonic antigen
  • low serum levels of IgA, IgG2 and/or IgE (in 70 percent of cases)
  • presence of spontaneous chromosome breaks and rearrangements in lymphocytes in vitro and in cultured fibroblasts
  • reduced survival of lymphocyte and fibroblast cultures after exposure to ionizing radiation

Laboratory Markers of A-T

Fortunately, any differential diagnostic difficulty should be easily resolved by reference to the laboratory. The most consistent laboratory marker of A-T is an elevated serum alphafetoprotein after the age of two years. Diagnostic support may also be offered by a finding of low serum IgA, IgG and/or IgE. However, these dysimmune findings vary from patient to patient and are not abnormal in all cases.

The presence of spontaneous chromosome breaks and rearrangements in lymphocytes in vitro and in cultured skin fibroblasts, although not invariably present, is also an important laboratory marker of A-T. And finally, reduced survival of lymphocyte and fibroblast cultures, after exposure to ionizing radiation, will confirm a diagnosis of A-T, although this technique is usually a research procedure and is not routinely available to the physician.

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