[Histological and radiobiological study on adult cases with ataxia telangiectasia]

Ataxia telangiectasia (AT) is a hereditary disease that involves both the immune and nervous system; its pathogenesis is believed to be due to disturbances in DNA repair system. Because children are usually affected, reports concerning adult patients are rare. In the present study, we performed comprehensive clinical, histological, and radiobiological examinations on two adult female siblings, currently 23 and 19 years old. The initial symptom was an ataxic gait, which began in the elder sister at the age of 20 and the younger sister at the age of 18. Both had mild telangiectasia in the bulbar conjunctiva and auricula. The neurological manifestations of both were gaze nystagmus, cerebellar ataxia, hyporeflexia, and vibratory sensation disturbance. Only the elder sister showed stocking type sensory disturbance. The MRI of both patients revealed cerebellar atrophy, especially in vermis. After either X-ray irradiation or bleomycin treatment, fibroblast survival curve showed a marked, dose-dependent declined in both patients compared with normal controls. Similar patterns were observed in both patients. After bleomycin treatment, no differences in the survival ratio of cultured fibroblasts could be found between these adult patients and those observed in younger children with classic AT. Biopsied sural nerves showed a decrease in the number of large myelinated fibers, with a few myelinated axons having relatively thin myelin. There were severe atrophic changes, with regenerative myelinated fibers in the elder sister. In conclusion, both adult patients with delayed onset AT displayed similar bleomycin hypersensitivity in fibroblasts as would be expected in children with AT. Radiobiological examinations and sural nerve biopsy suggest that both disturbed cellular regeneration and atrophic process may play a role in the neural involvement in this disease.