Abstract
Alexander disease (AxD) is a rare autosomal dominant leukodystrophy caused by heterozygous mutations in the glial fibrillary acid protein (GFAP) gene. The age of symptoms onset ranges from infancy to adulthood, with variable clinical and radiological manifestations. Adult-onset AxD manifests as a chronic and progressive condition, characterized by bulbar, motor, cerebellar, and other clinical signs and symptoms. Neuroradiological findings typically involve the brainstem and cervical spinal cord. Adult-onset AxD has been described in diverse populations but is rare in Israel. We present a series of patients diagnosed with adult-onset AxD from three families, all of Jewish Syrian descent. Five patients (4 females) were diagnosed with adult-onset AxD due to the heterozygous mutation c.219G > A, p.Met73Ile in GFAP. Age at symptoms onset ranged from 48 to 61 years. Clinical characteristics were typical and involved progressive bulbar and gait disturbance, followed by pyramidal and cerebellar impairment, dysautonomia, and cognitive decline. Imaging findings included medullary and cervical spinal atrophy and mostly infratentorial white matter hyperintensities. A newly recognized cluster of adult-onset AxD in Jews of Syrian origin is presented. This disorder should be considered in differential diagnosis in appropriate circumstances. Genetic counselling for family members is required in order to discuss options for future family planning.
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The data used to support the findings of this study are available from the corresponding author upon request.
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SA, SL, LG, and SHB played a key role in the conception and design of the study. SA, TFK, FS, and SHB monitored patients and provided valuable clinical insights. NM, OB, and DD conducted the genetic testing and bioinformatic analysis. OLS contributed to the interpretation of the neuroradiological data. OC, EP, and LG provided genetic expertise for the study. SA, LG, and SHB drafted the manuscript. All the authors critically reviewed the manuscript, provided input, and approved the final version.
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Anis, S., Fay-Karmon, T., Lassman, S. et al. Adult-onset Alexander disease among patients of Jewish Syrian descent. Neurogenetics 24, 303–310 (2023). https://doi.org/10.1007/s10048-023-00732-w
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DOI: https://doi.org/10.1007/s10048-023-00732-w