Hendriksz Christian J, Anheim Mathieu, Bauer Peter, Bonnot Olivier, Chakrapani Anupam, Corvol Jean-Christophe, de Koning Tom J, Degtyareva Anna, Dionisi-Vici Carlo, Doss Sarah, Duning Thomas, Giunti Paola, Iodice Rosa, Johnston Tracy, Kelly Dierdre, Klünemann Hans-Hermann, Lorenzl Stefan, Padovani Alessandro, Pocovi Miguel, Synofzik Matthis, Terblanche Alta, Then Bergh Florian, Topçu Meral, Tranchant Christine, Walterfang Mark, Velten Christian, Kolb Stefan A
a Salford Royal NHS Foundation Trust , Manchester , UK.
b University of Pretoria , Pretoria , South Africa.
Curr Med Res Opin. 2017 May;33(5):877-890. doi: 10.1080/03007995.2017.1294054. Epub 2017 Mar 2.
Niemann-Pick disease type C (NP-C) is a rare, inherited neurodegenerative disease of impaired intracellular lipid trafficking. Clinical symptoms are highly heterogeneous, including neurological, visceral, or psychiatric manifestations. The incidence of NP-C is under-estimated due to under-recognition or misdiagnosis across a wide range of medical fields. New screening and diagnostic methods provide an opportunity to improve detection of unrecognized cases in clinical sub-populations associated with a higher risk of NP-C. Patients in these at-risk groups ("clinical niches") have symptoms that are potentially related to NP-C, but go unrecognized due to other, more prevalent clinical features, and lack of awareness regarding underlying metabolic causes.
Twelve potential clinical niches identified by clinical experts were evaluated based on a comprehensive, non-systematic review of literature published to date. Relevant publications were identified by targeted literature searches of EMBASE and PubMed using key search terms specific to each niche. Articles published in English or other European languages up to 2016 were included.
Several niches were found to be relevant based on available data: movement disorders (early-onset ataxia and dystonia), organic psychosis, early-onset cholestasis/(hepato)splenomegaly, cases with relevant antenatal findings or fetal abnormalities, and patients affected by family history, consanguinity, and endogamy. Potentially relevant niches requiring further supportive data included: early-onset cognitive decline, frontotemporal dementia, parkinsonism, and chronic inflammatory CNS disease. There was relatively weak evidence to suggest amyotrophic lateral sclerosis or progressive supranuclear gaze palsy as potential niches.
Several clinical niches have been identified that harbor patients at increased risk of NP-C.
尼曼-匹克病C型（NP-C）是一种罕见的、遗传性的细胞内脂质转运受损的神经退行性疾病。临床症状高度异质性，包括神经、内脏或精神方面的表现。由于在广泛的医学领域中未被充分认识或误诊，NP-C的发病率被低估。新的筛查和诊断方法为改善在与NP-C高风险相关的临床亚人群中未被识别病例的检测提供了机会。这些高危人群（“临床细分群体”）中的患者有与NP-C潜在相关的症状，但由于其他更常见的临床特征以及对潜在代谢原因缺乏认识而未被识别。
基于对迄今发表文献的全面、非系统性综述，对临床专家确定的12个潜在临床细分群体进行评估。通过使用每个细分群体特有的关键搜索词在EMBASE和PubMed中进行针对性文献检索来识别相关出版物。纳入截至2016年以英文或其他欧洲语言发表的文章。
根据现有数据发现几个细分群体具有相关性：运动障碍（早发性共济失调和肌张力障碍）、器质性精神病、早发性胆汁淤积/（肝）脾肿大、有相关产前检查结果或胎儿异常的病例，以及受家族史、近亲结婚和族内通婚影响的患者。需要进一步支持性数据的潜在相关细分群体包括：早发性认知下降、额颞叶痴呆、帕金森症和慢性炎症性中枢神经系统疾病。有相对较弱的证据表明肌萎缩侧索硬化症或进行性核上性凝视麻痹是潜在的细分群体。
已确定了几个临床细分群体，其中的患者患NP-C的风险增加。
