Clinical disease characteristics of patients with Niemann-Pick Disease Type C: findings from the International Niemann-Pick Disease Registry (INPDR).
Clinical disease characteristics of patients with Niemann-Pick Disease Type C: findings from the International Niemann-Pick Disease Registry (INPDR).
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DOI：
10.1186/s13023-022-02200-4
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发表时间：
2022-02-14
影响因子：
3.7
通讯作者：
Geberhiwot T
中科院分区：
文献类型：
--
作者：
Bolton SC;Soran V;Marfa MP;Imrie J;Gissen P;Jahnova H;Sharma R;Jones S;Santra S;Crushell E;Stampfer M;Coll MJ;Dawson C;Mathieson T;Green J;Dardis A;Bembi B;Patterson MC;Vanier MT;Geberhiwot T
C型尼曼-皮克病（NPC）是一种常染色体隐性遗传的罕见疾病，其特征是进行性神经内脏表现。收集正在进行的大规模NPC临床数据可能会更好地了解疾病的自然史。在这里，我们报告了国际尼曼-匹克病登记处（INPDR）的NPC患者数据。 INPDR是一项基于网络、以患者为主导的独立登记研究，用于收集尼曼-匹克病患者的前瞻性和回顾性临床数据。提取了2014年9月至2019年12月入组INPDR的NPC患者的基线数据，以分析该疾病的人口统计学，遗传学和临床特征。共有来自6个欧洲国家的203名NPC患者被纳入本研究。诊断时的平均年龄（SD）为11.2岁（14.2）。在入组的患者中，168例有已知的神经系统表现：43例（24.2%）为婴儿早期发作，47例（26.4%）为婴儿晚期发作，41例（23.0%）为青少年发作，37例（20.8%）为成人发作。10例（5.6%）患者具有新生儿快速致死性全身形式。在97名具有已鉴定的NPC 1变异的患者中，最常见的变异是c。3182 T> C变异导致p.lle1061Thr蛋白变化，在35.1%（N = 34）的患者中报告。肝肿大和新生儿黄疸的发生率最高的患者与早期婴儿和晚期婴儿神经系统发病。脾肿大是最常报告的观察结果，包括80%的成人发病患者。最常见的神经系统表现为认知功能障碍（78.5%）、构音障碍（75.9%）、共济失调（75.9%）、垂直核上性凝视麻痹（70.9%）和吞咽困难（69.6%）。使用6域复合残疾量表计算每种神经系统形式的总体残疾评分。在所有神经系统发作的患者中，大多数患者在所有领域均表现出中度至重度损伤，但“吞咽”和“吞咽”除外。随着神经系统症状发作年龄的增加，诊断年龄和死亡年龄也增加。62.4%的患者记录了麦格司他的使用，患者使用的最常见对症治疗为抗癫痫药（32.9%）、抗抑郁药（11.8%）和抗酸药（9.4%）。在整个队列中，每个神经系统发病年龄的参与者比例相对相等。在所有年龄组中经常观察到神经系统表现，如共济失调、吞咽困难和构音障碍。
Niemann-Pick Disease Type C (NPC) is an autosomal recessive rare disease characterised by progressive neurovisceral manifestations. The collection of on-going large-scale NPC clinical data may generate better understandings of the natural history of the disease. Here we report NPC patient data from the International Niemann-Pick Disease Registry (INPDR). The INPDR is a web-based, patient-led independent registry for the collection of prospective and retrospective clinical data from Niemann-Pick Disease patients. Baseline data from NPC patients enrolled into the INPDR from September 2014 to December 2019 was extracted to analyse the demographic, genetic and clinical features of the disease. A total of 203 NPC patients from six European countries were included in this study. The mean age (SD) at diagnosis was 11.2 years (14.2). Among enrolled patients, 168 had known neurological manifestations: 43 (24.2%) had early-infantile onset, 47 (26.4%) had late-infantile onset, 41 (23.0%) had juvenile onset, and 37 (20.8%) had adult onset. 10 (5.6%) patients had the neonatal rapidly fatal systemic form. Among the 97 patients with identified NPC1 variants, the most common variant was the c. 3182T > C variant responsible for the p.lle1061Thr protein change, reported in 35.1% (N = 34) of patients. The frequencies of hepatomegaly and neonatal jaundice were greatest in patients with early-infantile and late-infantile neurological onset. Splenomegaly was the most commonly reported observation, including 80% of adult-onset patients. The most commonly reported neurological manifestations were cognitive impairment (78.5%), dysarthria (75.9%), ataxia (75.9%), vertical supranuclear gaze palsy (70.9%) and dysphagia (69.6%). A 6-domain composite disability scale was used to calculate the overall disability score for each neurological form. Across all with neurological onset, the majority of patients showed moderate to severe impairments in all domains, except for ‘swallowing’ and ‘seizure’. The age at diagnosis and death increased with increased age of neurological symptom onset. Miglustat use was recorded in 62.4% of patients and the most common symptomatic therapies used by patients were antiepileptics (32.9%), antidepressants (11.8%) and antacids (9.4%). The proportion of participants at each age of neurological onset was relatively equal across the cohort. Neurological manifestations, such as ataxia, dysphagia, and dysarthria, were frequently observed across all age categories.
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影响因子：
3.7
作者：
Geberhiwot T;Moro A;Dardis A;Ramaswami U;Sirrs S;Marfa MP;Vanier MT;Walterfang M;Bolton S;Dawson C;Héron B;Stampfer M;Imrie J;Hendriksz C;Gissen P;Crushell E;Coll MJ;Nadjar Y;Klünemann H;Mengel E;Hrebicek M;Jones SA;Ory D;Bembi B;Patterson M;International Niemann-Pick Disease Registry (INPDR)
通讯作者：
International Niemann-Pick Disease Registry (INPDR)
影响因子：
4.5
作者：
Lee, Su-Yun;Lee, Hyung Jin;Kim, Jae Woo
通讯作者：
Kim, Jae Woo
影响因子：
4.4
作者：
Iturriaga, C.;Pineda, M.;Coll, M. J.
通讯作者：
Coll, M. J.
影响因子：
3.9
作者：
Dardis, Andrea;Zampieri, Stefania;Bembi, Bruno
通讯作者：
Bembi, Bruno
影响因子：
3.7
作者：
Héron B;Valayannopoulos V;Baruteau J;Chabrol B;Ogier H;Latour P;Dobbelaere D;Eyer D;Labarthe F;Maurey H;Cuisset JM;de Villemeur TB;Sedel F;Vanier MT
通讯作者：
Vanier MT