The Diverse Neuromuscular Spectrum of VPS13A Disease.

IF 3.9 2区 医学 Q1 CLINICAL NEUROLOGY
Anne Buchberger, Evamaria Riedel, Marie Hackenberg, Alexander Mensch, Stefanie Beck-Woedl, Joohyun Park, Tobias B Haack, Bernhard Haslinger, Jan Kirschke, Holger Prokisch, Andreas Hermann, Christian Mawrin, Adrian Danek, Benedikt Schoser, Kevin Peikert, Marcus Deschauer, Isabell Cordts
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Abstract

Objective: VPS13A disease (chorea-acanthocytosis) is a rare neurodegenerative disorder caused by biallelic variants in VPS13A, typically presenting with hyperkinetic movement disorders, while neuromuscular signs are often mild. The aim of the project was to investigate the frequency and severity of neuromuscular impairment in VPS13A disease.

Methods: We systematically assessed the neuromuscular involvement in six patients with VPS13A disease. Our evaluation included genetic and clinical data, blood tests, electrophysiological studies, muscle MRI, and tissue samples from muscle and nerve.

Results: Age at clinical onset was 14 to 38 years (median: 37.5). Age at onset of paresis was 27 to 29 years (median: 29). Initial symptoms included seizures (5/6), hyperkinesia (2/6), and muscle weakness (1/6). Neuromuscular signs ranged from hyporeflexia (5/6) to progressive muscle wasting (3/6). Nine VPS13A variants were detected, including a novel copy-neutral inversion. Phosphocreatine kinase was elevated in all cases (498-12,420 U/L; median of highest values: 2230 U/L). Nerve conduction studies revealed sensorimotor axonal neuropathy. Electromyography showed chronic neurogenic changes with high amplitudes, polyphasic potentials, and reduced interference patterns (6/6). Muscle MRI displayed fatty atrophy, most prominently in the calves (5/5). Muscle histology indicated neurogenic and myopathic changes. Electron microscopy of mitochondria and respiratory chain analysis showed no specific pathological findings.

Interpretation: Our findings emphasize the underrecognized neuromuscular spectrum in VPS13A disease, ranging from subclinical signs to severe paresis and sometimes preceding the hyperkinesia that gave rise to the historical term of chorea-acanthocytosis. A comprehensive understanding of the phenotype is crucial for early diagnosis and appropriate management of VPS13A disease.

VPS13A疾病的不同神经肌肉谱。
目的:VPS13A病(舞蹈病-棘细胞增多症)是一种罕见的由VPS13A双等位基因变异引起的神经退行性疾病,典型表现为多动性运动障碍,而神经肌肉体征通常较轻。该项目的目的是调查VPS13A疾病中神经肌肉损伤的频率和严重程度。方法:系统评估6例VPS13A病患者的神经肌肉受累情况。我们的评估包括基因和临床数据、血液测试、电生理研究、肌肉MRI以及肌肉和神经组织样本。结果:临床发病年龄为14 ~ 38岁(中位:37.5岁)。发病年龄为27 ~ 29岁(中位:29岁)。最初症状包括癫痫发作(5/6)、运动亢进(2/6)和肌肉无力(1/6)。神经肌肉症状从反射减退(5/6)到进行性肌肉萎缩(3/6)。检测到9个VPS13A变体,包括一个新的复制中性反转。磷酸肌酸激酶在所有病例中均升高(498-12,420 U/L,最高值中位数为2230 U/L)。神经传导研究显示感觉运动轴索神经病。肌电图显示慢性神经源性改变,具有高振幅、多相电位和减少的干扰模式(6/6)。肌肉MRI显示脂肪萎缩,最明显的是小腿(5/5)。肌肉组织学显示神经源性和肌病性改变。线粒体电镜及呼吸链分析未见特殊病理表现。解释:我们的研究结果强调了VPS13A疾病中未被充分认识的神经肌肉谱,从亚临床症状到严重的轻瘫,有时在运动亢进之前,这导致了舞蹈病-棘细胞增多症的历史术语。全面了解表型对于VPS13A疾病的早期诊断和适当管理至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)
CiteScore
9.10
自引率
1.90%
发文量
218
审稿时长
8 weeks
期刊介绍: Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.
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