Mohamed Ibrahim Norlinah, Lin Chin Hsien
Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan; Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
Parkinsonism Relat Disord. 2024 Dec;129:107100. doi: 10.1016/j.parkreldis.2024.107100. Epub 2024 Aug 15.
Early Onset Parkinsonism (EOP) refers to parkinsonism occurring before the age of 50 years. The causes are diverse and include secondary and genetic causes. Secondary causes related to medications, inflammatory and infective disorders are mostly treatable and well recognized as they usually present with a relatively more rapid clinical course compared to idiopathic Parkinson's disease. Genetic causes of EOP are more challenging to diagnose especially as more of the non-PARK genes are recognized to present with typical and atypical parkinsonism. Some of the genetic disorders such as Spinocerebellar ataxia 2 (SCA2) and Spinocerebellar ataxia 3 (SCA3) may present with levodopa-responsive parkinsonism, indistinguishable from idiopathic Parkinson's disease. Additionally, some of the genetic disorders, including Wilson's disease and cerebrotendinous xanthomatosis (CTX), are potentially treatable and should not be missed. Due to the advent of next generating sequencing techniques, genetic analyses facilitate early identification and proper treatment of diverse causes of EOP. In this review, we outline the clinical approach of EOP highlighting the key clinical features of some of the non-PARK genetic causes of EOP and related investigations, which could assist in clinical diagnosis. This review also encompass genetic diagnostic approaches, emphasizing the significance of pretest counseling and the principles of bioinformatics analysis strategies.
早发性帕金森综合征（EOP）指的是在50岁之前出现的帕金森综合征。其病因多种多样，包括继发性和遗传性病因。与药物、炎症和感染性疾病相关的继发性病因大多是可治疗的，并且由于它们通常比特发性帕金森病呈现出相对更快的临床病程，因此广为人知。EOP的遗传病因更具诊断挑战性，尤其是随着越来越多的非PARK基因被发现可导致典型和非典型帕金森综合征。一些遗传性疾病，如脊髓小脑共济失调2型（SCA2）和脊髓小脑共济失调3型（SCA3），可能表现为对左旋多巴有反应的帕金森综合征，与特发性帕金森病难以区分。此外，一些遗传性疾病，包括威尔逊病和脑腱性黄瘤病（CTX），有可能得到治疗，不应被漏诊。由于新一代测序技术的出现，基因分析有助于早期识别和恰当治疗EOP的各种病因。在本综述中，我们概述了EOP的临床处理方法，重点介绍了EOP一些非PARK遗传病因的关键临床特征及相关检查，这有助于临床诊断。本综述还涵盖了基因诊断方法，强调了检测前咨询的重要性以及生物信息学分析策略的原则。
