Autopsy Report of a Woman with Infantile Alexander Disease Who Survived 39 Years

Abstract

AbstractPatients with infantile Alexander disease (AxD) usually do not survive beyond their early teens without life support care because of progressive central hypoventilation. We present the autopsy report of a woman with infantile AxD carrying an R239C mutation in the glial fibrillary acidic protein gene, who survived 39 years. She presented with psychomotor retardation in infancy and regressed after age 5. Brain computed tomography scans showed bilateral low frontal white matter density. She became quadriplegic with bulbar palsy and was intellectually handicapped after a measles infection at age 7. Tube feeding was introduced because of dysphagia at age 15. Noninvasive positive pressure ventilation was required due to central hypoventilation in her early thirties. She died of neurogenic respiratory failure at 39 years. Autopsy findings revealed a markedly atrophic brain (709 g, −6.0 standard deviation), especially in the frontal lobe, cerebellum, and brainstem portions. We found demyelination, gliosis, and cystic lesions throughout the brain, and we saw Rosenthal fibers accumulating in the perivascular spaces. We also identified a variety of abnormalities in other organs such as pancreatic necrosis, completely desquamated epithelium in the lower esophagus and stomach, foreign-body giant cells in the colon submucosa, glomerular sclerosis, and multiple bladder stones. This is the first autopsied case report of a patient with infantile AxD with long survival, who showed not only central nervous system characteristic findings, but also unexpected pathological changes in other organs.