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Neurology. 2018 Sep 4;91(10):e917-e930. doi: 10.1212/WNL.0000000000006121. Epub 2018 Aug 10.

Nonataxia symptoms in Friedreich Ataxia: Report from the Registry of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS).

Author information

1
From the Department of Neurology (K.R., I.D., C.H., C.D., J.B.S.), RWTH Aachen University; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging (K.R., I.D., C.H., C.D., J.B.S.), Forschungszentrum Jülich GmbH and RWTH Aachen University, Germany; Department of Molecular Neuroscience (P.G.), Ataxia Center, UCL Institute of Neurology, London, UK; Unit of Genetics of Neurodegenerative and Metabolic Diseases (C.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; ICM (Brain and Spine Institute) Sorbonne Universités (A.D.), UPMC Univ Paris 06 UMR S 1127, and INSERM U 1127, CNRS UMR 7225 and APHP, Pitié-Salpêtrière University Hospital, Genetic Department, Paris, France; Department of Neurology (S.B.), Medical University Innsbruck, Austria; Department of Neurology (T.K.), Friedrich Baur Institute, University Hospital of the Ludwig-Maximilians-Universität München; German Center for Neurodegenerative Diseases (DZNE) (T.K.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich, Germany; Reference Unit of Hereditary Ataxias and Paraplegias (F.J.R.d.R.G.), Department of Neurology, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain; Department of Neurodegenerative Diseases (L.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (I.G.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G.), Bonn; Department of Neurology (K.B.), Philipps University of Marburg, Germany; and Laboratory of Experimental Neurology (M.P.), Université Libre de Bruxelles, Brussels, Belgium.
2
From the Department of Neurology (K.R., I.D., C.H., C.D., J.B.S.), RWTH Aachen University; JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging (K.R., I.D., C.H., C.D., J.B.S.), Forschungszentrum Jülich GmbH and RWTH Aachen University, Germany; Department of Molecular Neuroscience (P.G.), Ataxia Center, UCL Institute of Neurology, London, UK; Unit of Genetics of Neurodegenerative and Metabolic Diseases (C.M.), Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; ICM (Brain and Spine Institute) Sorbonne Universités (A.D.), UPMC Univ Paris 06 UMR S 1127, and INSERM U 1127, CNRS UMR 7225 and APHP, Pitié-Salpêtrière University Hospital, Genetic Department, Paris, France; Department of Neurology (S.B.), Medical University Innsbruck, Austria; Department of Neurology (T.K.), Friedrich Baur Institute, University Hospital of the Ludwig-Maximilians-Universität München; German Center for Neurodegenerative Diseases (DZNE) (T.K.), Munich; Munich Cluster for Systems Neurology (SyNergy) (T.K.), Munich, Germany; Reference Unit of Hereditary Ataxias and Paraplegias (F.J.R.d.R.G.), Department of Neurology, IdiPAZ, Hospital Universitario La Paz, Madrid, Spain; Department of Neurodegenerative Diseases (L.S.), Hertie-Institute for Clinical Brain Research, University of Tübingen; Department of Neurology (I.G.), University Hospital of Bonn; German Center for Neurodegenerative Diseases (DZNE) (I.G.), Bonn; Department of Neurology (K.B.), Philipps University of Marburg, Germany; and Laboratory of Experimental Neurology (M.P.), Université Libre de Bruxelles, Brussels, Belgium. jschulz@ukaachen.de.

Abstract

OBJECTIVE:

To provide a systematic evaluation of the broad clinical variability in Friedreich ataxia (FRDA), a multisystem disorder presenting mainly with afferent ataxia but also a complex phenotype of nonataxia symptoms.

METHODS:

From the large database of the European Friedreich's Ataxia Consortium for Translational Studies, 650 patients with genetically confirmed FRDA were included. Detailed data of medical history documentation, questionnaires, and reports on clinical features were analyzed to provide in-depth description of the clinical profile and frequency rates of phenotypical features with a focus on differences between typical-onset and late-onset FRDA. Logistic regression modeling was used to identify predictors for the presence of the most common clinical features.

RESULTS:

The most frequent clinical features beyond afferent ataxia were abnormal eye movements (90.5%), scoliosis (73.5%), deformities of the feet (58.8%), urinary dysfunction (42.8%), cardiomyopathy and cardiac hypertrophy (40.3%), followed by decreased visual acuity (36.8%); less frequent features were, among others, depression (14.1%) and diabetes (7.1%). Most of these features were more common in the typical-onset group compared to the late-onset group. Logistic regression models for the presence of these symptoms demonstrated the predictive value of GAA repeat length on the shorter allele and age at onset, but also severity of ataxia signs, sex, and presence of neonatal problems.

CONCLUSIONS:

This joint European effort demonstrates the multisystem nature of this neurodegenerative disease encompassing most the central nervous, neuromuscular, cardiologic, and sensory systems. A distinct and deeper knowledge of this rare and chronic disease is highly relevant for clinical practice and designs of clinical trials.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02069509.

PMID:
30097477
DOI:
10.1212/WNL.0000000000006121
[Indexed for MEDLINE]

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