Ataxia Telangiectasia (AT) as a radiation sensitivity syndrom and limits of radiotherapeutic intervention

Aims: Ataxia Telangiectasia (AT) is an autosomal recessive inherited ataxia and results from a mutation within the ATM (Ataxia Telangiectasia Mutated)-gene. Functional consequences of this mutation lead to a multisystemic disorder with severe and progressive neurodegeneration, ocular and cutaneous telangiectasia, increased irradiation-sensitivity and a tendency to develop malignant diseases. Clinicians face a difficult challenge regarding the treatment of oncological diseases within AT-patients as guidelines on radiotherapeutic management and dosis-toxicity-limits are missing. We present the long term changes of a patient with missed diagnosis of AT who received whole brain radiation due to early childhood – ALL. We outline the causality regarding AT as a radiation sensitivity syndrom and direct therapeutic toxicity. Methods: The 7 year old patient with missed diagnosis of AT suffered from ALL at the age of 3, received whole brain radiation (12Gy), and chemotherapy. We are comparing clinical und neuroradiological results of this boy with the results of his also from AT suffering brother, who never received chemo- or radio therapy. Results: The patient with radiation therapy presented with severe telangiectasia of his skull, lack of hair growth, prominent ocular telangiectasia, cataract, mental retardation and severe changes in cranial imaging (empty sella, microhaemorrhages, caveromas, leukencephalopathic white-matter lesions (WML). Conclusion: AT is a disease with dysfunctionality of the ATM-kinase. Most important tasks of the ATM-kinase are initiating DNA-damage repair and the activation of tumor suppressor genes. Functional deficits within ATM lead to elevated radiation sensitivity and tumor disposition. Additional exposure of AT-patients to increased radiation may be disastrous. As guidelines on radiotherapeutic management of oncologic AT-patients are barely existent we recommend the measurement of serum AFP-protein in pediatric oncologic patients with undetermined movement disorders in order to avoid long-term radiation induced complications within yet undiagnosed AT-patients. Ataxia-Telangiectasia - Louis-Bar-Syndrom - telangiectasia - irratiation-sensitivity - oncology