Clinical, genetic, and advanced neuroimaging features in adult siblings with Q10 deficiency due to COQ4 mutation: Review of literature.

OBJECTIVE

To describe two adult siblings with a COQ4 gene mutation presenting with progressive ataxia and discuss advanced magnetic resonance imaging (MRI) findings. MATERIALS AND

METHODS

A 34-year-old woman and her 29-year-old brother, underwent standardized neurological evaluation and MRI including structural sequences with volumetric morphometry, diffusion tensor imaging (DTI) tractography, arterial spin-labeling (ASL) perfusion, and resting-state functional MRI (rs-fMRI). Targeted genetic testing was performed. Clinical follow-up after initiation of CoQ10 supplementation was recorded.

RESULTS

Genetic analysis identified a homozygous pathogenic COQ4 variant in both patients. Brain MRI in both cases demonstrated moderate cerebellar atrophy and bilateral occipital lobe FLAIR hyperintensities. Volumetric analysis confirmed reduced cerebellar volumes and cortical thickness in several lobules. DTI showed significantly decreased fractional anisotropy in multiple white matter tracts. rs-fMRI analysis corroborated structural findings, showing diminished connectivity from posterior cerebellar lobules to occipital and parietal cortices, consistent with the patients’ visuomotor impairment. ASL perfusion maps demonstrated diffuse cerebral hypoperfusion, most pronounced in occipital cortices that showed FLAIR hyperintensity, indicating mitochondria-related flow compromise. Symptomatic treatment with high-dose coenzyme Q10 (200 mg TID) and vitamin E, plus rehabilitation, led to partial improvement in balance at 6-month follow-up, although ataxia persisted.

CONCLUSIONS

COQ4-related CoQ10 deficiency can manifest in adulthood with occipital-predominant signal abnormalities and cerebellar ataxy. Multimodal MRI (DTI, ASL, rs-fMRI) captures convergent structural, perfusion, and connectivity disturbances consistent with the mitochondrial stroke-like spectrum. Early recognition of these imaging patterns may facilitate diagnosis, counseling, and follow-up.