Effects of idursulfase enzyme replacement therapy for Mucopolysaccharidosis type II when started in early infancy: Comparison in two siblings
Effects of idursulfase enzyme replacement therapy for Mucopolysaccharidosis type II when started in early infancy: Comparison in two siblings
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DOI：
10.1016/j.ymgme.2012.12.010
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发表时间：
2013-03-01
影响因子：
3.8
通讯作者：
Kobayashi, Masao
中科院分区：
文献类型：
--
作者：
Tajima, Go;Sakura, Nobuo;Kobayashi, Masao
II 型粘多糖贮积症 (MPS II) 是一种进行性的溶酶体贮积症，涉及多个器官和组织。虽然艾杜硫酶酶替代疗法 (ERT) 已被证明可以改善该疾病的许多躯体特征，但一些疾病，如多发性骨发育不全和心脏瓣膜疾病，一旦建立就显得不可逆转，而且人们对 ERT 对症状前患者的预防作用知之甚少。我们报道了两个患有严重 MPS II 的兄弟姐妹，该突变是由 IDS 基因及其相邻假基因 IDS-2 内的重组断点的倒位突变引起的。兄弟姐妹在 3.0 岁时（哥哥）和 4 个月（弟弟）开始接受艾杜硫酶治疗，我们比较了他们治疗 2 年后的结果。治疗开始时，哥哥表现出 MPS II 的典型特征，包括智力障碍。经过 34 个月的 ERT 治疗后，他的躯体疾病稳定或有所改善，但他的认知能力继续下降。相比之下，经过 32 个月的 ERT 治疗后，他的弟弟仍然没有出现他弟弟同龄时出现的大部分躯体特征，仅表现为渗出性中耳炎。骨骼X光检查显示哥哥在治疗开始时患有多发性骨不全的特征性症状，两年后没有变化，而弟弟在整个治疗期间仅表现出轻微的多发性骨不全的表现。随着时间的推移，弟弟的发育商数呈下降趋势，略低于正常范围。这些发现表明，症状前开始 ERT 可能会预防或减弱 MPS II 躯体特征的进展。需要对大量患者进行随访，以确认 ERT 对症状前患者的额外长期益处。 (C) 2013 Elsevier Inc. 保留所有权利。
Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder that is progressive and involves multiple organs and tissues. While enzyme replacement therapy (ERT) with idursulfase has been shown to improve many somatic features of the disease, some such as dysostosis multiplex and cardiac valve disease appear irreversible once established, and little is known about the preventative effects of ERT in pre-symptomatic patients. We report on two siblings with severe MPS II caused by an inversion mutation with recombination breakpoints located within the IDS gene and its adjacent pseudogene, IDS-2. The siblings initiated treatment with idursulfase at 3.0 years (older brother) and 4 months (younger brother) of age, and we compared their outcomes following 2 years of treatment. At the start of treatment, the older brother showed typical features of MPS II, including intellectual disability. After 34 months of ERT, his somatic disease was stable or improved, but he continued to decline cognitively. By comparison, after 32 months of ERT his younger brother remained free from most of the somatic features that had already appeared in his brother at the same age, manifesting only exudative otitis media. Skeletal X-rays revealed characteristic signs of dysostosis multiplex in the older brother at the initiation of treatment that were unchanged two years later, whereas the younger brother showed only slight findings of dysostosis multiplex throughout the treatment period. The younger brother's developmental quotient trended downward over time to just below the normal range. These findings suggest that pre-symptomatic initiation of ERT may prevent or attenuate progression of the somatic features of MPS II. Follow-up in a larger number of patients is required to confirm the additive long-term benefits of ERT in pre-symptomatic patients. (C) 2013 Elsevier Inc. All rights reserved.