Department of Neurodegenerative Diseases, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Cerebellum. 2012 Dec;11(4):1002-11. doi: 10.1007/s12311-012-0378-2.
Mutations in the mitochondrial DNA polymerase gamma (POLG) cause a highly pleomorphic disease spectrum, and reports about their frequencies in ataxia populations yield equivocal results. This leads to uncertainties about the role of POLG genetics in the workup of patients with unexplained ataxia. A comprehensive characterization of POLG-associated ataxia (POLG-A) will help guide genetic diagnostics and advance our understanding of the disease processes underlying POLG-A. Thirteen patients with POLG-A were assessed by standardized clinical investigation, nerve conduction studies, motor-evoked potentials, magnetic resonance imaging (MRI) and transcranial sonography (TCS). The findings were compared with 13 matched patients with Friedreich's ataxia (FA). In addition to the well-known POLG-associated features of chronic external ophthalmoplegia (100 %), areflexia to the lower extremity (100 %), impaired vibration sense (100 %), bilateral ptosis (69 %) and epilepsy (38 %), also hyperkinetic movement disorders were frequent in POLG-A patients, including chorea (31 %), dystonia (31 %) and myoclonus (23 %). Similar to FA, polyneuropathy was of sensory axonal type (100 %). In contrast to FA, none of the POLG-A patients showed impaired central motor conduction. TCS demonstrated less enlargement of the fourth ventricle and more diffuse cerebellar hyperechogenicity in POLG-A. Corresponding to TCS, MRI revealed no or only mild cerebellar atrophy in most POLG-A patients (85 %). POLG ataxia presents with the clinical characteristics of both afferent and cerebellar ataxia. Cerebellar alterations diffusely involve various parts of the cerebellum, yet cerebellar atrophy is generally mild. POLG-A presents with a high load of distinct non-ataxia features, namely, sensory neuropathy, external ophthalmoplegia, ptosis, epilepsy and/or hyperkinetic movement disorders. Involvement of the corticospinal tract, however, is rare.
线粒体 DNA 聚合酶 γ（POLG）突变导致高度多形性疾病谱，并且关于其在共济失调人群中的频率的报告结果不一致。这导致在未明确病因的共济失调患者的检查中，对 POLG 遗传学作用存在不确定性。对 POLG 相关共济失调（POLG-A）进行全面描述将有助于指导遗传诊断并深入了解 POLG-A 相关疾病过程。通过标准化临床检查、神经传导研究、运动诱发电位、磁共振成像（MRI）和经颅超声（TCS）评估了 13 名 POLG-A 患者。将这些发现与 13 名匹配的弗里德里希共济失调（FA）患者进行了比较。除了众所周知的 POLG 相关特征，慢性外眼肌麻痹（100%）、下肢反射消失（100%）、振动觉受损（100%）、双侧上睑下垂（69%）和癫痫（38%）外，POLG-A 患者还经常出现多动障碍，包括舞蹈症（31%）、肌张力障碍（31%）和肌阵挛（23%）。与 FA 相似，多发性神经病为感觉轴索性（100%）。与 FA 不同，POLG-A 患者中没有一个存在中央运动传导受损。TCS 显示 POLG-A 中第四脑室扩张较小，小脑弥漫性高回声增强。与 TCS 相对应，MRI 显示大多数 POLG-A 患者（85%）小脑无或仅有轻度萎缩。POLG 共济失调表现为传入性和小脑性共济失调的临床特征。小脑改变广泛涉及小脑的各个部位，但小脑萎缩通常较轻。POLG-A 表现出多种独特的非共济失调特征，即感觉性神经病、外眼肌麻痹、上睑下垂、癫痫和/或多动障碍。皮质脊髓束受累则很少见。
