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Abstract：
Perry disease (or Perry syndrome) is an autosomal dominant neurodegenerative disorder characterized by parkinsonism, neuropsychiatric symptoms, central hypoventilation, weight loss and distinct TDP-43 pathology. It is caused by mutations of the DCTN1 gene encoding an essential component of axonal transport. The objectives were to provide the current state of knowledge on clinical, pathological and genetic aspects of Perry disease, as well as practical suggestions for the management of the disease.
Data on new patients from New Zealand, Poland and Colombia were collected, including autopsy report. Also all of the published papers since the original work by Perry in 1975 were gathered and analyzed.
Parkinsonism was symmetrical, progressed rapidly and was poorly responsive to L-Dopa; nonetheless, a trial with high doses of L-Dopa is warranted. Depression was severe, associated with suicidal ideations, and benefited from antidepressants and L-Dopa. Respiratory symptoms were the leading cause of death, and artificial ventilation or a diaphragm pacemaker prolonged survival. Weight loss occurred in most patients and was of multifactorial etiology. Autonomic dysfunction was frequent but underdiagnosed. There was a clinical overlap with other neurodegenerative disorders. An autopsy showed distinctive pallidonigral degeneration with TDP-43 pathology. Genetic testing provided evidence of a common founder for two families. There was striking phenotypic variability in DCTN1-related disorders. It is hypothesized that oligogenic or polygenic inheritance is at play.
Perry disease and other DCTN1-related diseases are increasingly diagnosed worldwide. Relatively effective symptomatic treatments are available. Further studies are needed to pave the way toward curative/gene therapy.
Data on new patients from New Zealand, Poland and Colombia were collected, including autopsy report. Also all of the published papers since the original work by Perry in 1975 were gathered and analyzed.
Parkinsonism was symmetrical, progressed rapidly and was poorly responsive to L-Dopa; nonetheless, a trial with high doses of L-Dopa is warranted. Depression was severe, associated with suicidal ideations, and benefited from antidepressants and L-Dopa. Respiratory symptoms were the leading cause of death, and artificial ventilation or a diaphragm pacemaker prolonged survival. Weight loss occurred in most patients and was of multifactorial etiology. Autonomic dysfunction was frequent but underdiagnosed. There was a clinical overlap with other neurodegenerative disorders. An autopsy showed distinctive pallidonigral degeneration with TDP-43 pathology. Genetic testing provided evidence of a common founder for two families. There was striking phenotypic variability in DCTN1-related disorders. It is hypothesized that oligogenic or polygenic inheritance is at play.
Perry disease and other DCTN1-related diseases are increasingly diagnosed worldwide. Relatively effective symptomatic treatments are available. Further studies are needed to pave the way toward curative/gene therapy.
摘要：
佩里病（或佩里综合征）是一种常染色体显性遗传的神经退行性疾病，以帕金森病为特征，神经精神症状,中枢通气不足,体重减轻和明显的TDP-43病理。它是由编码轴突运输必需成分的DCTN1基因突变引起的。目的是提供临床知识的现状，佩里病的病理和遗传方面，以及对疾病管理的实用建议。
来自新西兰的新患者数据，波兰和哥伦比亚被收集，包括验尸报告.此外，收集并分析了自1975年Perry的原始作品以来发表的所有论文。
帕金森病是对称的，进展迅速，对左旋多巴反应不佳；尽管如此，有必要进行高剂量左旋多巴的试验.抑郁症很严重,与自杀意念有关，并受益于抗抑郁药和左旋多巴。呼吸道症状是导致死亡的主要原因,和人工通气或隔膜起搏器延长生存期。体重减轻发生在大多数患者中，并且是多因素病因。自主神经功能障碍是常见的，但未被诊断。与其他神经退行性疾病有临床重叠。尸检显示TDP-43病理具有独特的苍白质变性。基因检测提供了两个家庭共同创始人的证据。DCTN1相关疾病的表型变异显著。假设寡基因或多基因遗传在起作用。
佩里病和其他DCTN1相关疾病在全球范围内的诊断越来越多。相对有效的对症治疗是可用的。需要进一步的研究为治愈/基因治疗铺平道路。
来自新西兰的新患者数据，波兰和哥伦比亚被收集，包括验尸报告.此外，收集并分析了自1975年Perry的原始作品以来发表的所有论文。
帕金森病是对称的，进展迅速，对左旋多巴反应不佳；尽管如此，有必要进行高剂量左旋多巴的试验.抑郁症很严重,与自杀意念有关，并受益于抗抑郁药和左旋多巴。呼吸道症状是导致死亡的主要原因,和人工通气或隔膜起搏器延长生存期。体重减轻发生在大多数患者中，并且是多因素病因。自主神经功能障碍是常见的，但未被诊断。与其他神经退行性疾病有临床重叠。尸检显示TDP-43病理具有独特的苍白质变性。基因检测提供了两个家庭共同创始人的证据。DCTN1相关疾病的表型变异显著。假设寡基因或多基因遗传在起作用。
佩里病和其他DCTN1相关疾病在全球范围内的诊断越来越多。相对有效的对症治疗是可用的。需要进一步的研究为治愈/基因治疗铺平道路。
