Miglustat therapy in the French cohort of paediatric patients with Niemann-Pick disease type C.
Miglustat therapy in the French cohort of paediatric patients with Niemann-Pick disease type C.
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DOI：
10.1186/1750-1172-7-36
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发表时间：
2012-06-07
影响因子：
3.7
通讯作者：
Vanier MT
中科院分区：
文献类型：
--
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
C型尼曼-匹克病（NP-C）是一种罕见的神经内脏溶酶体脂质沉积病，其特征是进行性神经功能恶化。关于麦格司他在临床实践环境中用于儿科患者的已发表数据有限。我们报告了一项在法国儿科NP-C队列中进行的前瞻性开放标签研究的结果。汇编了2006年10月至2010年12月期间法国接受麦格司他治疗的所有儿童NP-C患者的数据。所有患者均确诊为NP-C，并根据生产商的建议接受麦格司他治疗。根据标准化方案进行治疗前和随访评估。20名儿童入组; 19名有NPC 1基因突变，1名有NPC 2基因突变。诊断时的中位年龄为1.5岁，麦格司他开始治疗时的中位年龄为6.0岁。8名NPC 1患者患有早期婴儿型，8名患有晚期婴儿型，3名患有幼年型NP-C。在所有8例早期婴儿型患者、3/8例晚期婴儿型患者和1/3例青少年型患者中记录了肝脾肿大和/或其他胆汁淤积症状病史。脑成像显示大多数患者存在白色异常。麦格司他治疗的中位（范围）持续时间在婴儿早期为1.3（0.6-2.3）年，婴儿晚期为1.0（0.8-5.0）年，青少年发作患者为1.0（0.6-2.5）年。NP-C残疾量表评分分别表明这些亚组中1/8、6/8和1/3例NPC 1患者的神经系统表现稳定或改善。脑影像学表现与病程无相关性。在麦格司他治疗的前3个月内，轻至中度胃肠道紊乱较为常见，但可通过饮食调整和/或抗推进药物轻松管理。麦格司他可改善或稳定婴儿晚期和青少年发作型NP-C儿科患者的神经系统表现。在婴儿早发患者中，神经系统疾病发作与麦格司他开始治疗之间的延迟较短与1例患者的初始治疗结局较好相关，但麦格司他似乎未改变该亚组的总体病程。需要在从神经系统表现一开始就接受治疗的婴儿期早发患者中获得更多的麦格司他长期治疗经验。
Niemann-Pick disease type C (NP-C) is a rare neurovisceral lysosomal lipid storage disease characterized by progressive neurological deterioration. Published data on the use of miglustat in paediatric patients in clinical practice settings are limited. We report findings from a prospective open-label study in the French paediatric NP-C cohort. Data on all paediatric NP-C patients treated with miglustat in France between October 2006 and December 2010 were compiled. All patients had a confirmed diagnosis of NP-C, and received miglustat therapy according to manufacturer’s recommendations. Pre-treatment and follow-up assessments were conducted according to a standardized protocol. Twenty children were enrolled; 19 had NPC1 gene mutations and 1 had NPC2 gene mutations. The median age at diagnosis was 1.5 years, and the median age at miglustat initiation was 6.0 years. Eight NPC1 patients had the early-infantile, eight had the late-infantile, and three had the juvenile-onset forms of NP-C. A history of hepatosplenomegaly and/or other cholestatic symptoms was recorded in all 8 early-infantile onset patients, 3/8 late-infantile patients, and 1/3 juvenile onset patients. Brain imaging indicated white matter abnormalities in most patients. The median (range) duration of miglustat therapy was 1.3 (0.6–2.3) years in early-infantile, 1.0 (0.8–5.0) year in late-infantile, and 1.0 (0.6–2.5) year in juvenile onset patients. NP-C disability scale scores indicated either stabilization or improvement of neurological manifestations in 1/8, 6/8, and 1/3 NPC1 patients in these subgroups, respectively. There were no correlations between brain imaging findings and disease course. Mild-to-moderate gastrointestinal disturbances were frequent during the first 3 months of miglustat therapy, but were easily managed with dietary modifications and/or anti-propulsive medication. Miglustat can improve or stabilize neurological manifestations in paediatric patients with the late-infantile and juvenile-onset forms of NP-C. Among early-infantile onset patients, a shorter delay between neurological disease onset and miglustat initiation was associated with an initial better therapeutic outcome in one patient, but miglustat did not seem to modify overall disease course in this subgroup. More experience is required with long-term miglustat therapy in early-infantile onset patients treated from the very beginning of neurological manifestations.
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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：
3.8
作者：
Pineda, M.;Wraith, J. E.;Patterson, M. C.
通讯作者：
Patterson, M. C.
影响因子：
11
作者：
Tedeschi, G;Bonavita, S;Schiffmann, R
通讯作者：
Schiffmann, R
影响因子：
3.8
作者：
Patterson, Marc C.;Hendriksz, Christian J.;Wijburg, Frits
通讯作者：
Wijburg, Frits
影响因子：
9.8
作者：
Millat, G;Marçais, C;Vanier, MT
通讯作者：
Vanier, MT