Diagnosing Alexander disease in adults
- PMID: 40350261
- DOI: 10.1136/pn-2024-004490
Diagnosing Alexander disease in adults
Abstract
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.
Keywords: CLINICAL NEUROLOGY; MOVEMENT DISORDERS; MRI; NEUROGENETICS; NEURORADIOLOGY.
© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.
Conflict of interest statement
Competing interests: DSL is a consultant and scientific advisor to Eli Lilly and Vigil Neuroscience. AKC has received research support from Biogen and Genentech; has served on scientific advisory boards for Bristol Myers Squibb and Sanofi; and has served as a consultant for Icometrix, Ionis, Novartis and Vigil Neuro. FB is a steering committee or data safety monitoring board member for ATRI/ACTS, Biogen, Merck and Prothena; serves as a consultant for Celltrion, Combinostics, IXICO, Janssen, Merck, Rewind Therapeutics and Roche; he also has research agreements with Biogen, GE Healthcare, Merck and Roche; and is a cofounder and shareholder of Queen Square Analytics Ltd. AC and MRE are employees of and hold stock in Ionis. ATW has received grant funding from the NIH (U54NS115052); she has also received research funding for investigator-initiated research from Elise’s Corner, Grayson’s Ladder, Ionis and the United Leukodystrophy Foundation; she has received clinical trial support from Ionis and (unrelated to this work) Novartis, Passage Bio, Pfizer, Roche/Genentech and Sarepta. She has served as a non-remunerated scientific advisor for Elise’s Corner and The Calliope Joy Foundation; receives honoraria from MedLink Neurology and UpToDate and received personal compensation for serving on a data safety monitoring board from SwanBio. All other authors report no competing interests.