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.
Neurology. 2018 Sep 4;91(10):e917-e930. doi: 10.1212/WNL.0000000000006121. Epub 2018 Aug 10.
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.
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.
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.
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.
系统评估弗里德赖希共济失调（FRDA）的广泛临床变异性，FRDA 是一种多系统疾病，主要表现为传入性共济失调，但也有非共济失调症状的复杂表型。
从欧洲弗里德赖希共济失调转化研究联合会的大型数据库中，纳入了 650 名经基因证实的 FRDA 患者。对病史记录、问卷调查和临床特征报告的详细数据进行分析，深入描述临床特征谱和表型特征的频率，并重点关注典型发病和迟发性 FRDA 之间的差异。使用逻辑回归模型来确定最常见临床特征存在的预测因素。
除传入性共济失调外，最常见的临床特征是眼球运动异常（90.5%）、脊柱侧凸（73.5%）、足部畸形（58.8%）、尿功能障碍（42.8%）、心肌病和心脏肥大（40.3%），其次是视力下降（36.8%）；较少见的特征包括抑郁症（14.1%）和糖尿病（7.1%）。这些特征在典型发病组中比在迟发性发病组中更为常见。用于存在这些症状的逻辑回归模型表明，较短等位基因和发病年龄、共济失调体征严重程度、性别以及新生儿问题的 GAA 重复长度具有预测价值。
这项欧洲联合研究表明，这种神经退行性疾病具有多系统性质，涉及中枢神经系统、神经肌肉、心脏和感觉系统。深入了解这种罕见和慢性疾病对于临床实践和临床试验设计具有重要意义。
