Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.
J Inherit Metab Dis. 2013 Jan;36(1):129-37. doi: 10.1007/s10545-012-9479-9. Epub 2012 Apr 5.
Niemann-Pick disease type C (NP-C) is a rare inherited neurovisceral disease characterized by progressive neurological manifestations. Oral miglustat was first approved for the treatment of children and adults with NP-C in Europe in 2009. There are still relatively few published data on the long-term efficacy and safety of miglustat in patients with NP-C in clinical practice. We report the effects of up to 6 years of treatment with miglustat 100 mg t.i.d. in five children. Overall, 3/5 patients displayed progressive dysphagia before starting miglustat, and 4/5 showed marked cognitive and/or motor impairment. The mean age at treatment start was 11.6 years, and the median (range) duration of therapy so far is 4 (4.1 to 6.1) years. No treatment dose alterations were required, but therapy was interrupted for 1-3 months at least once in all patients due to supply issues. Swallowing function was stabilised during miglustat therapy, with no significant increase in Han dysphagia scale or aspiration-penetration index scores among four evaluable patients (p > 0.05). Scores on the mini-mental state examination indicated an improvement in cognitive function during the first 3-6 months of miglustat therapy, followed by stabilisation up to 5 years. Ambulatory function remained stable for at least the first 2 years of treatment in most patients, but there was a trend towards deterioration thereafter, possibly related to treatment interruptions. The safety/tolerability profile of miglustat was similar to previous clinical studies, although reports of gastrointestinal disturbances were rare. Overall, miglustat appeared to stabilise key parameters of neurological disease progression.
尼曼-匹克病 C 型(NP-C)是一种罕见的遗传性神经内脏疾病,其特征为进行性神经表现。米格列醇于 2009 年在欧洲首次被批准用于治疗 NP-C 儿童和成人。在临床实践中,关于米格列醇治疗 NP-C 患者的长期疗效和安全性的相关数据仍然较少。我们报告了 5 例儿童接受米格列醇 100mg,每日 3 次治疗长达 6 年的效果。总体而言,3/5 例患者在开始米格列醇治疗前出现进行性吞咽困难,4/5 例患者表现出明显的认知和/或运动障碍。治疗开始时的平均年龄为 11.6 岁,迄今为止的中位(范围)治疗持续时间为 4(4.1 至 6.1)年。无需调整治疗剂量,但由于供应问题,所有患者均至少中断治疗 1-3 个月。吞咽功能在米格列醇治疗期间得到稳定,4 例可评估患者的汉吞咽困难量表或吸入-渗透指数评分无显著增加(p>0.05)。迷你精神状态检查评分表明,在米格列醇治疗的前 3-6 个月认知功能有所改善,随后稳定至少 5 年。大多数患者在治疗的最初 2 年内步行功能保持稳定,但此后有恶化趋势,可能与治疗中断有关。米格列醇的安全性/耐受性与之前的临床研究相似,尽管胃肠道紊乱的报告罕见。总体而言,米格列醇似乎稳定了神经疾病进展的关键参数。