Hearing loss in infantile Pompe's disease and determination of underlying pathology in the knockout mouse
Hearing loss in infantile Pompe's disease and determination of underlying pathology in the knockout mouse
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DOI：
10.1016/j.nbd.2003.12.018
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发表时间：
2004-06-01
影响因子：
6.1
通讯作者：
Reuser, AJJ
中科院分区：
文献类型：
--
作者：
Kamphoven, JHJ;de Ruiter, MM;Reuser, AJJ
听力缺陷发生在几种溶酶体贮积症中，但迄今为止尚未被认为是庞贝病（糖原贮积病 II 型）的症状。我们出人意料地发现，四名患有庞贝氏症的婴儿听力损失达 30-90 分贝，这些婴儿参加了一项酶替代疗法的安全性和有效性研究。另外三名青少年庞贝氏症患者没有这种症状。 ABR（听觉脑干反应）阈值增加，但峰间潜伏时间没有增加。这表明中耳或内耳病变，而不是中枢听觉神经系统的参与。没有耳声发射，支持可能发生耳蜗病理。我们在庞贝氏病基因敲除小鼠模型中研究了这一假设，发现耳蜗的内毛细胞和外毛细胞、支持细胞、血管纹和螺旋神经节细胞中存在糖原储存。我们得出结论，耳蜗病理是婴儿庞贝氏病听力损失的最可能原因，也可能是该临床亚型的特征。 (C) 2004 Elsevier Inc. 保留所有权利。
Hearing deficit occurs in several lysosomal storage disorders but has so far not been recognized as a symptom of Pompe's disease (glycogen storage disease type II). We discovered quite unexpectedly 30-90 dB hearing loss in four infants with Pompe's disease, who participated in a study on the safety and efficacy of enzyme replacement therapy. Three other patients with juvenile Pompe's disease did not have this symptom. The ABR (auditory brainstem response) thresholds but not the interpeak latency times were increased. This pointed to middle or inner ear pathology rather than to involvement of the central auditory nervous system. The possible occurrence of cochlear pathology was supported by the absence of oto-acoustic emissions. We investigated this hypothesis in a knockout mouse model of Pompe's disease and found glycogen storage in the inner and outer hair cells of the cochlea, the supporting cells, the stria vascularis, and the spiral ganglion cells.We conclude that cochlear pathology is the most likely cause of hearing loss in infantile Pompe's disease and possibly a characteristic feature of this clinical subtype. (C) 2004 Elsevier Inc. All rights reserved.