Unit of Rare Diseases, Department of Pediatrics, Gaslini Institute, Genoa, Italy.
Pediatr Neurol. 2012 Jul;47(1):40-3. doi: 10.1016/j.pediatrneurol.2012.04.005.
Niemann-Pick disease type C is a rare inherited cholesterol trafficking disorder, where impaired intracellular lipid transport leads to storage of unesterified cholesterol and glycosphingolipids in many tissues, including the brain. Substrate reduction therapy with miglustat, an iminosugar that inhibits glycosphingolipid synthesis, was proposed to treat Niemann-Pick disease type C, based on evidence of slower disease progression and prolonged survival in animal models. Miglustat was subsequently approved in Europe to treat progressive neurologic manifestations in both children and adults in early 2009, based on clinical study data. We report on the early treatment of two pediatric Niemann-Pick type C patients with miglustat. Patient 1, a 7.5-year-old girl with early-infantile onset, began receiving miglustat at age 7 months. Patient 2, the brother of a girl diagnosed with late-infantile onset Niemann-Pick type C, began receiving miglustat at age 19 months, when he was asymptomatic for neurologic disease. After 7 and 5 years of miglustat therapy, respectively, both patients remain free of neurologic manifestations. These findings suggest that miglustat may be more effective if used to prevent, rather than treat, neurologic manifestations in infantile-onset Niemann-Pick type C.
尼曼-匹克病 C 型是一种罕见的遗传性胆固醇转运障碍，其特征是细胞内脂质转运受损，导致未酯化胆固醇和糖鞘脂在包括大脑在内的许多组织中蓄积。基于动物模型中疾病进展减缓以及生存时间延长的证据，用米格列醇（一种抑制糖鞘脂合成的亚氨基糖）进行底物还原治疗被提议用于治疗尼曼-匹克病 C 型。随后，根据临床研究数据，米格列醇于 2009 年初在欧洲获准用于治疗儿童和成人的进行性神经表现。我们报告了用米格列醇对两名儿科尼曼-匹克 C 型患者的早期治疗情况。患者 1 为 7.5 岁女孩，起病于婴儿早期，于 7 个月大时开始接受米格列醇治疗。患者 2 是一名女孩的弟弟，该女孩被诊断为晚发性婴儿尼曼-匹克 C 型，于 19 个月大时无症状性神经疾病时开始接受米格列醇治疗。分别接受米格列醇治疗 7 年和 5 年后，两名患者均未出现神经表现。这些发现表明，米格列醇如果用于预防而非治疗婴儿起病型尼曼-匹克 C 型的神经表现，可能更有效。
