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Diagnosing A-T -- A Note to
Physicians
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 cases
of 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 A-T cases 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 age s 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.
And, 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.
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. |
