Retrospective cohort study reveals high diagnostic yields for exome sequencing in sporadic ataxia, highlighting critical barriers to genetic testing in public healthcare.
Key Points
To describe the 20-year diagnostic trajectory, genetic yield, and clinical outcomes for patients presenting with hereditary ataxia without a vertical family history.
Retrospective cohort study of 174 patients evaluated between 2002 and 2020 at a university hospital reference center in South Brazil.
Stepwise diagnostic protocol evaluating brain imaging, alpha-fetoprotein, Friedreich ataxia testing, ataxia Sanger panels, and next-generation exome or genome sequencing.
Of 120 patients returning for follow-up visits, 45 (37.5%) achieved a confirmed diagnosis, 12 (10.0%) completed testing without a diagnosis, and 63 (52.5%) had incomplete workups.
Diagnostic yields across advanced sequencing methods were 71.4% (5/7) for Sanger panels, 52.9% (9/17) for exome sequencing, and 14.0% (1/7) for whole-genome sequencing.
Most frequent diagnoses included Friedreich ataxia, ataxia-telangiectasia, Coenzyme Q10 deficiency, Niemann-Pick type C, and spinocerebellar ataxia type 2.