Chien Y-H, Lee N-C, Tsai L-K, Huang A-C, Peng S-F, Chen S-J, Hwu W-L
Department of Medical Genetics and Pediatrics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
J Inherit Metab Dis. 2007 Oct;30(5):826. doi: 10.1007/s10545-007-0630-y. Epub 2007 Jun 21.
Niemann-Pick disease type C (NP-C) is a lipid storage disorder characterized by the accumulation of unesterified cholesterol and glycolipids in the lysosomal/late endosomal system of certain cells in the central nervous system (CNS) and visceral organs. Clinical symptoms include progressive neurological deterioration and visceral organomegaly. Miglustat, a small iminosugar molecule approved for the treatment of Gaucher disease, reversibly inhibits glucosylceramide synthase, which catalyses the first committed step in glycosphingolipid synthesis. The physicochemical properties of miglustat allow it to cross the blood-brain barrier and suggest possible benefits in lysosomal storage diseases affecting the CNS. Here, we present findings in two children with NP-C, aged 14 years (patient 1) and 9 years (patient 2), treated with miglustat for 1 year. Before treatment, patient 1 presented with severe difficulties in swallowing and walking, and patient 2 with problems mostly affecting communication and social interaction. Videofluoroscopic studies in patient 1 demonstrated a substantial improvement in swallowing by month 6 of treatment, and ambulation index measurements indicated improved walking. Mini Mental-State Examination (MMSE) assessments in patient 2 showed cognitive improvement by month 6, which was sustained up to month 12. Liver/spleen volume and plasma chitotriosidase activities were stabilized in both cases. There was no weight loss during treatment. Patient 1 experienced severe but self-limiting paresthesia, which was not associated with peripheral neuropathy. We conclude that miglustat can provide therapeutic benefits in CNS symptoms and allows stabilization of systemic disease in childhood-onset NP-C. Further follow-up is crucial to determine the long-term maintenance of these effects.
尼曼-匹克病C型（NP-C）是一种脂质贮积病，其特征是未酯化胆固醇和糖脂在中枢神经系统（CNS）和内脏器官某些细胞的溶酶体/晚期内体系统中蓄积。临床症状包括进行性神经功能恶化和内脏器官肿大。米格列醇是一种已被批准用于治疗戈谢病的小亚氨基糖分子，它可逆性抑制葡糖神经酰胺合酶，该酶催化糖鞘脂合成的首个关键步骤。米格列醇的物理化学性质使其能够穿过血脑屏障，并提示其可能对影响中枢神经系统的溶酶体贮积病有益。在此，我们报告了两名分别为14岁（患者1）和9岁（患者2）的NP-C患儿接受米格列醇治疗1年的研究结果。治疗前，患者1存在严重的吞咽和行走困难，患者2的问题主要影响沟通和社交互动。对患者1进行的电视荧光透视研究显示，治疗6个月时吞咽功能有显著改善，步行指数测量表明行走能力有所提高。对患者2进行的简易精神状态检查表（MMSE）评估显示，治疗6个月时认知功能有所改善，并持续至12个月。两例患者的肝/脾体积和血浆壳三糖苷酶活性均稳定。治疗期间体重未减轻。患者1经历了严重但自限性的感觉异常，这与周围神经病变无关。我们得出结论，米格列醇可改善中枢神经系统症状，并能稳定儿童期发病的NP-C的全身性疾病。进一步随访对于确定这些疗效的长期维持情况至关重要。
