Early Onset Ataxia with Comorbid Dystonia: Clinical, Anatomical and Biological Pathway Analysis Expose Shared Pathophysiology.

摘要: In degenerative adult onset ataxia (AOA), dystonic comorbidity is attributed to one disease continuum. However, in early (EOA), the prevalence and pathogenesis of (EOAD+), are still unclear. 80 EOA-patients, we determined EOAD+-prevalence association with MRI-abnormalities. Subsequently, explored underlying biological pathways by genetic network functional enrichment analysis. We checked pathway-outcomes specific EOAD+-genotypes comparing results non-specifically (in-silico-determined) shared genes up-to-date EOA, AOA dystonia gene panels (that could concurrently cause dystonia). majority (65%) mild EOAD+-features concurred extra-cerebellar MRI abnormalities (at pons and/or basal-ganglia thalamus (p = 0.001)). Genetic analysis indicated an organelle- cellular-component organization (important for energy production signal transduction). non-specifically, in-silico-determined genes, were enriched Krebs-cycle fatty acid/lipid-metabolic processes. frequently occurring EOAD+-phenotypes, clinical, anatomical pathway analyses reveal pathophysiology between dystonia, associated cellular metabolism transduction. Insight heterogeneous EOAD+-phenotype-genotype relationships supports rationale testing complete, movement disorder lists, instead single EOA gene-panels.