# Adult-Onset Alexander Disease: A Case Report and Literature Review of Glu207 Alterations

## TL;DR

A 67-year-old woman with adult-onset Alexander disease had a rare GFAP gene mutation, showing how genetic testing and imaging can help diagnose this rare neurological disorder.

## Contribution

This case expands the known genetic variants of adult-onset Alexander disease and highlights the importance of GFAP testing in adults with unexplained neurological symptoms.

## Key findings

- A heterozygous GFAP c.620A>T (p.Glu207Val) variant was identified in a patient with adult-onset Alexander disease.
- Characteristic MRI findings included spinal cord atrophy and periventricular FLAIR hyperintensity.
- The mutation was present in a symptomatic sibling and maternal relatives, supporting autosomal dominant inheritance with variable expressivity.

## Abstract

Alexander disease (AxD) is a rare leukodystrophy caused by heterozygous mutations in GFAP. We report the case of a 67-year-old woman with progressive dysarthria, dysphagia, ataxia, and oculomotor dysfunction. MRI revealed medullary and cervical spinal cord atrophy with a periventricular T2/fluid-attenuated inversion recovery (FLAIR) hyperintense rim, findings characteristic of adult-onset AxD. Genetic testing identified a heterozygous GFAP c.620A>T (p.Glu207Val) variant, absent from major population databases. Her symptomatic brother carried the same mutation, and additional maternal relatives exhibited suggestive neurological features, supporting autosomal dominant inheritance with variable expressivity. In silico tools predicted the variant to be pathogenic, and multiple mutations at the same residue have been associated with AxD. This case expands the genotypic spectrum of adult-onset AxD, reinforces the diagnostic value of characteristic imaging findings, and underscores the importance of considering GFAP testing in adults with unexplained bulbar and pyramidal signs. Early recognition facilitates targeted symptomatic management and informs genetic counseling in affected families.