Vroegindeweij Lena H P, Langendonk Janneke G, Langeveld Mirjam, Hoogendoorn Mels, Kievit Anneke J A, Di Raimondo Domenico, Wilson J H Paul, Boon Agnita J W
Department of Internal Medicine, Centre for Lysosomal and Metabolic Diseases, Erasmus MC Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands.
Department of Hematology, Medical Centre Leeuwarden, PO Box 888, 8901 BR Leeuwarden, The Netherlands.
Parkinsonism Relat Disord. 2017 Mar;36:33-40. doi: 10.1016/j.parkreldis.2016.12.010. Epub 2016 Dec 15.
The diagnosis aceruloplasminemia is usually made in patients with advanced neurological manifestations of the disease. In these patients prognosis is poor, disabilities are severe and patients often die young. The aim of our study was to facilitate recognition of aceruloplasminemia at a disease stage at which treatment can positively influence outcome. Currently, the neurological phenotype of aceruloplasminemia has been mainly described in Japanese patients. This 'classical' phenotype consists of cerebellar ataxia, hyperkinetic movement disorders and cognitive decline. In this study we describe the spectrum of neurological disease in Caucasian patients.
Data on neurological presentation and follow-up were gathered from both our patients, homozygous for the G631R mutation in the CP gene, and other published Caucasian cases. Neurological features of aceruloplasminemia in Caucasian patients were compared to those summarized in Japanese patients.
21 Caucasian patients, both ours and the described cases, displayed a wide range of movement disorders with predominant chorea, parkinsonism and ataxia, and also tremor and dystonia. In addition to cognitive decline, nearly half of the Caucasian patients presented with psychiatric changes, including depression, anxiety and behavioral changes. In one-third of the neurologically symptomatic Caucasian patients, cognitive- or psychiatric changes were the first neurological manifestations of aceruloplasminemia.
Aceruloplasminemia in Caucasian patients can present with a wider range and a different order of neurological symptoms than previously described in Japanese patients. Psychiatric changes and parkinsonism can be added to the spectrum of neurological disease. Cognitive- or psychiatric changes may be the first neurological manifestations of aceruloplasminemia.
血浆铜蓝蛋白缺乏症的诊断通常在疾病出现晚期神经症状的患者中做出。这些患者预后较差，残疾严重，且往往英年早逝。我们研究的目的是在疾病阶段促进对血浆铜蓝蛋白缺乏症的识别，此时治疗可对结果产生积极影响。目前，血浆铜蓝蛋白缺乏症的神经表型主要在日本患者中得到描述。这种“经典”表型包括小脑共济失调、运动亢进性运动障碍和认知衰退。在本研究中，我们描述了白种人患者的神经疾病谱。
收集了我们的患者（CP基因G631R突变纯合子）以及其他已发表的白种人病例的神经症状表现和随访数据。将白种人患者血浆铜蓝蛋白缺乏症的神经特征与日本患者总结的特征进行比较。
我们的患者及已描述病例中的21名白种人患者表现出广泛的运动障碍，以舞蹈症、帕金森综合征和共济失调为主，还伴有震颤和肌张力障碍。除认知衰退外，近一半的白种人患者出现精神变化，包括抑郁、焦虑和行为改变。在三分之一有神经症状的白种人患者中，认知或精神变化是血浆铜蓝蛋白缺乏症的首发神经表现。
白种人患者的血浆铜蓝蛋白缺乏症可能呈现出比日本患者先前描述的更广泛且不同顺序的神经症状。精神变化和帕金森综合征可加入神经疾病谱。认知或精神变化可能是血浆铜蓝蛋白缺乏症的首发神经表现。
