Mayo Clinic, Rochester, MN, USA.
Orphanet J Rare Dis. 2013 Jan 16;8:12. doi: 10.1186/1750-1172-8-12.
Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterized by progressive neurodegeneration and premature death. We report data recorded at enrolment in an ongoing international NP-C registry initiated in September 2009 to describe disease natural history, clinical course and treatment experience of NP-C patients in clinical practice settings.
The NPC Registry is a prospective observational cohort study. Participating sites are encouraged to evaluate all consecutive patients with a confirmed diagnosis of NP-C, regardless of their treatment status. All patients undergo clinical assessments and medical care as determined by their physicians. Data are collected through a secure internet-based data collection system.
As of 19th March, 2012, 163 patients have been enrolled in centres across 14 European countries, Australia, Brazil and Canada. The mean (SD) age at enrolment was 19.6 (13.0) years. In general there was a long lag time between the mean (SD) age at neurological onset (10.9 (9.8) years) and age at diagnosis (15.0 (12.2) years). Among all enrolled patients, 107 were diagnosed based on combined genetic testing and filipin staining. Sixteen (11%) out of 145 patients with available age-at-neurological-onset data had early-infantile neurological onset, 45 (31%) had late-infantile onset; 45 (31%) had juvenile onset and 39 (27%) had adolescent/adult onset. The frequencies of neonatal jaundice, hepatomegaly and/or splenomegaly during infancy were greatest among early-infantile patients, and decreased with increasing age at neurological onset. The most frequent neurological manifestations were: ataxia (70%), vertical supranuclear gaze palsy (VSGP; 70%), dysarthria (66%), cognitive impairment (62%), dysphagia (52%). There were no notable differences in composite NP-C disability scores between age-at-neurological-onset groups. Miglustat therapy at enrolment was recorded in 117/163 (72%) patients.
Approximately two-thirds of this NP-C cohort had infantile or juvenile onset of neurological manifestations, while the remaining third presented in adolescence or adulthood. While systemic symptoms were most common among patients with early-childhood onset disease, they were also common among patients with adolescent/adult onset. The profiles of neurological manifestations in this Registry were in line with previous publications.
尼曼-匹克病 C 型（NP-C）是一种罕见的神经内脏疾病，其特征为进行性神经退行性变和过早死亡。我们报告了 2009 年 9 月启动的一项正在进行的 NP-C 国际登记处的数据，该登记处旨在描述 NP-C 患者在临床实践环境中的疾病自然史、临床过程和治疗经验。
NP-C 登记处是一项前瞻性观察队列研究。鼓励参与地点评估所有确诊为 NP-C 的连续患者，无论其治疗状况如何。所有患者都接受医生确定的临床评估和医疗护理。数据通过安全的基于互联网的数据收集系统收集。
截至 2012 年 3 月 19 日，已在 14 个欧洲国家、澳大利亚、巴西和加拿大的 163 个中心招募了患者。登记时的平均（标准差）年龄为 19.6（13.0）岁。一般来说，从神经发病的平均（标准差）年龄（10.9（9.8）岁）到诊断年龄（15.0（12.2）岁）之间存在较长的滞后时间。在所有登记的患者中，有 107 人根据联合基因检测和 filipin 染色诊断。在 145 名具有可用神经发病年龄数据的患者中，有 16 名（11%）为早发性婴儿期神经发病，45 名（31%）为晚发性婴儿期发病；45 名（31%）为少年发病，39 名（27%）为青少年/成年发病。在早发性婴儿期患者中，新生儿黄疸、肝脾肿大的频率最高，且随着神经发病年龄的增加而降低。最常见的神经系统表现为：共济失调（70%）、垂直核上性眼球运动麻痹（70%）、构音障碍（66%）、认知障碍（62%）、吞咽困难（52%）。在神经发病年龄组之间，NP-C 综合残疾评分没有显著差异。在 163 名患者中，有 117 名（72%）患者在登记时接受了米格列醇治疗。
大约三分之二的 NP-C 患者在婴儿期或少年期出现神经表现，其余三分之一在青少年期或成年期发病。虽然早发性疾病患者的全身症状最为常见，但在青少年/成年发病患者中也很常见。该登记处的神经系统表现特征与以往文献报道一致。
