Alexander disease

Alexander disease (also known as Alexander's disease, fibrinoid leukodystrophy, or dysmyelinogenic leukodystrophy) is a rare progressive neurological disorder belonging to the group of leukodystrophies — diseases that affect the white matter of the brain. It is caused by mutations in the GFAP gene, which encodes glial fibrillary acidic protein, a major intermediate filament protein in astrocytes. These mutations lead to a gain-of-function effect that causes astrocyte dysfunction and the accumulation of characteristic cytoplasmic inclusions called Rosenthal fibers throughout the central nervous system. The disease primarily affects the brain and spinal cord. The most common and severe form is the infantile type, which typically presents before age two with progressive megalencephaly (abnormally enlarged head), seizures, spasticity, psychomotor regression, and developmental delay. Frontal predominant white matter abnormalities are a hallmark finding on brain MRI. A juvenile form presents in later childhood with bulbar and pseudobulbar signs, ataxia, spasticity, and progressive cognitive decline. An adult-onset form also exists, which may present with palatal myoclonus, dysphagia, dysphonia, ataxia, spasticity, and autonomic dysfunction, often with brainstem and spinal cord atrophy on imaging. There is currently no cure or disease-modifying treatment for Alexander disease. Management is supportive and symptomatic, including antiepileptic medications for seizure control, physical and occupational therapy, nutritional support, and management of spasticity. Prognosis varies significantly by age of onset: the infantile form is typically the most severe, often leading to death within the first decade of life, while juvenile and adult forms may have a more protracted course. Research into potential therapies, including antisense oligonucleotides targeting GFAP, is ongoing.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Alexander disease