Diagnosis And Treatment

The diagnosis of AT in index cases is typically delayed until telangiectasias appear at 6 or 7 years of age (6). However, the absence of telangiectasias, immune deficits, and/or elevated serum AFP do not rule out AT as a diagnosis for the toddler or young child with slowly progressive ataxia. The size of the ATM gene and the large number and even distribution of mutations along the ATM gene make molecular diagnosis difficult (see Fig. 3). As a result, sequential evaluation of children suspected of having AT is recommended, beginning with a clinical assessment of neurologic and immunologic deficits accompanied by serum AFP determination and karyotype. Further investigations include protein truncation testing and Western blot analyses of ATM protein, measurement of ATM kinase activity, colony-survival assays using lymphocytes and SSCP analysis of the ATM gene. This combined approach is thought to yield a false-negative rate of <1% (190).

Improvements in supportive care have increased the quality of life for AT patients and extended their expected life span. However, despite major strides in our understanding of the ATM gene and the molecular basis of AT, therapy still focuses on symptomatic relief of neurologic and immunologic problems rather than treatment of underlying deficits (191). Although antioxidants, L-dopa, gene therapy, and neuronal transplants all have been considered as potential therapies, effective treatments have yet to emerge from our new knowledge of AT pathobi-ology. The recent establishment of an Ataxia-Telangiectasia Clinical Center at Johns Hopkins in Baltimore has already led to large-scale studies of the course of the disease and, in the future, may facilitate clinical trials that could lead to the development of new ways to treat this devastating condition (http://ww2.med.jhu. edu/ataxia/clinicar.htm).

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