{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T05:20:33Z","timestamp":1782796833057,"version":"3.54.5"},"reference-count":19,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T00:00:00Z","timestamp":1678924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Friedreich's ataxia (FRDA), most commonly caused by a GAA triplet repeat (GAA\u2010TR) expansion in intron 1 of the <jats:italic>FXN<\/jats:italic> gene, is characterized by deficiency of frataxin protein and clinical features such as progressive ataxia, dysarthria, impaired proprioception and vibration, abolished deep tendon reflexes, Babinski sign, and vision loss in association with non\u2010neurological features such as skeletal anomalies, hearing loss, cardiomyopathy, and diabetes. Pathogenic GAA\u2010TRs range in size from 60 to 1500 triplets and negatively correlate with age of onset. Clinical severity is predicted by a combination of GAA\u2010TR length and disease duration (DD) via multivariable regressions, which cannot typically be used for the small sample sizes in most studies on this rare disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to develop a single metric, which we call \u201cdisease burden\u201d (DB), that encompasses both GAA\u2010TR length and DD for predicting disease features of FRDA in small sample sizes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Linear regression and multivariable regression analysis was used to determine correlation coefficients between different disease features of FRDA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using large datasets for validation, we found that DB predicts measures of neurological dysfunction in FRDA better than GAA\u2010TR length or DD. Analogous results were found using small datasets.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>FRDA DB is a novel metric of disease severity that has utility in small datasets to demonstrate correlations that would not otherwise be evident with either GAA\u2010TR or DD alone. This is important for discovering new biomarkers, as well as improving the prediction of severity of disease features in FRDA. \u00a9 2023 International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29370","type":"journal-article","created":{"date-parts":[[2023,3,17]],"date-time":"2023-03-17T00:38:50Z","timestamp":1679013530000},"page":"970-977","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A Novel Metric for Predicting Severity of Disease Features in Friedreich's Ataxia"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2826-0395","authenticated-orcid":false,"given":"Layne N.","family":"Rodden","sequence":"first","affiliation":[{"name":"Departments of Pediatrics and Neurology, Children's Hospital of Philadelphia, Perelman School of Medicine University of Pennsylvania  Philadelphia Pennsylvania 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