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High diagnostic value of plasma Niemann-Pick type C biomarkers in adults with selected neurological and/or psychiatric disorders.
Journal of Neurology ( IF 4.8 ) Pub Date : 2020-06-26 , DOI: 10.1007/s00415-020-10020-4
Daniele Mandia 1 , Marion Plaze 2 , Isabelle Le Ber 3, 4 , Claire Ewenczyk 5 , Alexandre Morin 4 , Guilhem Carle 6 , Angèle Consoli 7 , Adrian Degardin 8 , Ali Amad 9 , Caroline Moreau 10 , Mathieu Anheim 11, 12, 13 , Christine Tranchant 11, 12, 13 , Nicolas Mélé 14 , Carole Roue-Jagot 15 , Julien Lagarde 15 , Marie Sarazin 15 , Lorraine Hamelin 15 , Pierre Ellul 16 , Cécile Pagan 17 , Magali Pettazzoni 17 , Soumeya Bekri 18 , Serge Belliard 19 , Cyril Goizet 20 , David Wallon 21 , Foudil Lamari 22 , Yann Nadjar 1
Affiliation  

Late-onset Niemann-Pick type C (NP-C) is a rare, underdiagnosed lysosomal disease with neurological manifestations. A specific treatment, miglustat, can stabilize the disease if given early. Recently, three plasma screening biomarkers (PSBs) were developed [cholestane3β,5α,6βtriol (C-triol), 7-ketocholesterol (7-KC), and lysosphingomyelin-509 (LSM-509)], allowing a simpler and quite robust screening of patients suitable for genetic testing. The objective of our study was to evaluate practical utility and feasibility of large-scale PSB screening for NP-C in selected adult patients. Patients were prospectively enrolled if they showed, starting from 12 years of age, at least one of the three initial neuro-psychiatric manifestations described in NP-C: (1) gait disorder (cerebellar and/or dystonic); (2) cognitive decline with frontal lobe syndrome; (3) atypical psychosis. PSBs were measured in plasma of all patients and, if positive (LSM-509 and/or C-triol + 7-KC elevated), sequencing of NPC1 and NPC2 genes was performed. A total of 251 patients [136 males, 115 females; median age 42.1 (range 12.2–85.6) years] were screened. Six patients had positive PSBs. Two were confirmed to have NP-C (0.8% diagnostic yield, both with all three PSBs highly increased, especially LSM-509). False-positive rate was 1.2%, which was identical if only considering LSM-509. By contrast, false-positive rates were 8.1% and 5.7% for 7-KC and C-triol, respectively. We showed that selecting patients with neurologic and/or psychiatric symptoms consistent with NP-C for large-scale PSB screening is a simple and valid strategy to identify new adult NP-C patients, and would probably lead to earlier diagnosis and treatment administration if widely applied.



中文翻译:

血浆Niemann-Pick C型生物标志物在患有特定神经系统和/或精神疾病的成年人中具有较高的诊断价值。

迟发性尼曼-匹克C型(NP-C)是一种罕见的,诊断不足的溶酶体病,具有神经系统表现。如果尽早给予特定的治疗,米格司他,可以使疾病稳定。最近,开发了三种血浆筛选生物标记物(胆甾烷3β,5α,6β三醇(C-三醇),7-酮胆固醇(7-KC)和溶血鞘磷脂-509(LSM-509)],从而可以进行更简单,更可靠的筛选适合基因测试的患者。我们研究的目的是评估在选定的成年患者中进行大规模PSB筛查NP-C的实用性和可行性。如果患者从12岁开始表现出NP-C中描述的三种最初的神经精神病学表现中的至少一种,则前瞻性入组:(1)步态障碍(小脑和/或肌张力障碍);(2)额叶综合征伴认知功能减退;(3)非典型精神病。测量所有患者血浆中的PSB,如果阳性(LSM-509和/或C-triol + 7-KC升高),则对进行了NPC1NPC2基因。总计251位患者[136例男性,115例女性;筛选年龄中位数为42.1岁(范围为12.2-85.6)]。6名患者PSB阳性。证实其中两个具有NP-C(诊断产率为0.8%,所有三个PSB均高度升高,尤其是LSM-509)。假阳性率为1.2%,如果仅考虑LSM-509,则为假阳性。相比之下,7-KC和C-三醇的假阳性率分别为8.1%和5.7%。我们表明,选择具有与NP-C一致的神经系统和/或精神病学症状的患者进行大规模PSB筛查是识别新的成年NP-C患者的简单有效的策略,如果广泛使用,可能会导致早期诊断和治疗应用。

更新日期:2020-06-26
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