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The Scale for the Assessment and Rating of Ataxia showed a mean annual increase of 1.02\u2009\u00b1\u20090.78 points\/year. Disease progression was faster in patients with age at onset \u2264\u200930\u2009years (1.5 Scale for the Assessment and Rating of Ataxia points\/year) than with later onset (0.5 points\/year); <jats:italic>P<\/jats:italic>\u00a0=\u00a00.008. The Inventory of Non\u2010Ataxia Symptoms count increased by 0.30\u2009\u00b1\u20090.4 points\/year. External ophthalmoplegia, brain stem oculomotor signs, areflexia, and sensory deficits were the most common nonataxic features. On MRI cerebellar atrophy was mild. T2 signal alterations affected mostly cerebellar white matter, middle cerebellar peduncles, thalamus, brain stem, and occipital and frontal white matter. Within 4\u2009years, progression was primarily observed in the context of repeated epileptic seizures. Nerve conduction studies revealed axonal sensory peripheral neuropathy with mild motor nerve involvement. Exploratory sample size calculation implied 38 patients per arm as sufficient to detect a reduction of progression by 50% in hypothetical interventions within a 1\u2010year trial.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results recommend the Scale for the Assessment and Rating of Ataxia as a primary outcome measure for future interventional trials in polymerase gamma\u2013related ataxia. \u00a9 2021 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.28713","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T08:42:14Z","timestamp":1626770534000},"page":"2642-2652","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Natural History of Polymerase Gamma\u2013Related 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