Diagnosing Alexander disease in adults

Alexander disease is a rare, genetic and ultimately fatal neurological disorder that arises from pathogenic variants in the glial fibrillary acidic protein (GFAP) gene. Its presenting symptoms often differ according to age at onset. Although Alexander disease typically presents in young children with seizures and developmental delays, its presentation in adults may include bulbar signs, ataxia and autonomic dysfunction. Because of the heterogeneous and non-specific symptoms associated with adult-onset Alexander disease, the diagnosis typically requires comprehensive clinical and neuroimaging evaluation as well as confirmatory genetic testing. Here, we present detailed case descriptions of patients who first presented with symptoms of Alexander disease as adults, with guidance on recognising distinctive clinical and radiological characteristics associated with the later-onset form. Timely recognition and referral of patients with Alexander disease will enable earlier interventions that may mitigate disease severity or slow disease progression if such interventions become available.