Imaging Characteristics in the Ataxia-Neuropathy Spectrum Related to POLG Mutation

Abstract

Mutations in the mitochondrial DNA polymerase gamma (POLG) gene cause a broad spectrum of neurodegenerative disorders, including the ataxia-neuropathy spectrum (ANS). Substantial phenotypic heterogeneity and overlapping clinical features can delay diagnosis. We report a 38-year-old woman with no significant past medical history who presented with a three-year history of slowly progressive sensory ataxia that worsened in the dark. Examination revealed mild dysarthria, large-fiber sensory loss, and a positive Romberg sign. Extensive metabolic, toxic, autoimmune, and infectious work-up was unrevealing. Nerve conduction studies confirmed a mild peripheral sensory neuropathy. Brain magnetic resonance imaging (MRI) demonstrated distinct bilateral, symmetric T2-weighted and fluid-attenuated inversion recovery (FLAIR) hyperintensities in the dorsomedial thalami and cerebellar white matter. Whole-exome sequencing confirmed a homozygous W748S mutation in the POLG gene, establishing a diagnosis of POLG-related ANS. This imaging pattern, though not specific to POLG-related disease, may support earlier consideration of targeted genetic testing when present alongside a compatible clinical picture.