The respiratory neuromuscular system in Pompe disease.
The respiratory neuromuscular system in Pompe disease.
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DOI：
10.1016/j.resp.2013.06.007
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发表时间：
2013-11-01
影响因子：
2.3
通讯作者：
Byrne, Barry J.
中科院分区：
文献类型：
--
作者：
Fuller, David D.;ElMallah, Mai K.;Smith, Barbara K.;Corti, Manuela;Lawson, Lee Ann;Falk, Darin J.;Byrne, Barry J.
庞贝氏症是由于编码溶酶体酶酸性α-葡糖苷酶（GAA）的基因突变所致。缺乏功能性GAA通常会导致第一年的心肺功能衰竭; GAA活性降低与生命后期的进行性呼吸衰竭相关。虽然骨骼肌病理导致庞贝氏症的呼吸功能不全，但新出现的证据表明呼吸神经元功能障碍也是运动单位功能障碍的重要组成部分。动物模型显示，脊髓和延髓呼吸神经元中有大量糖原积累，神经活动发生改变。庞贝氏症患者的组织显示中枢神经系统糖原积聚和运动神经元病理学。神经机制引起了对酶替代的当前临床方法的考虑，因为重组蛋白不穿过血脑屏障。事实上，临床数据表明，酶替代疗法可以延缓症状进展，但许多患者最终需要辅助治疗，特别是在睡眠期间。我们建议，治疗恢复GAA活性的呼吸肌，神经元和网络将需要完全纠正在庞贝氏症的排尿功能不全。
Pompe disease is due to mutations in the gene encoding the lysosomal enzyme acid α-glucosidase (GAA). Absence of functional GAA typically results in cardiorespiratory failure in the first year; reduced GAA activity is associated with progressive respiratory failure later in life. While skeletal muscle pathology contributes to respiratory insufficiency in Pompe disease, emerging evidence indicates that respiratory neuron dysfunction is also a significant part of dysfunction in motor units. Animal models show profound glycogen accumulation in spinal and medullary respiratory neurons and altered neural activity. Tissues from Pompe patients show central nervous system glycogen accumulation and motoneuron pathology. A neural mechanism raises considerations about the current clinical approach of enzyme replacement since the recombinant protein does not cross the blood-brain-barrier. Indeed, clinical data suggest that enzyme replacement therapy delays symptom progression, but many patients eventually require ventilatory assistance, especially during sleep. We propose that treatments which restore GAA activity to respiratory muscles, neurons and networks will be required to fully correct ventilatory insufficiency in Pompe disease.
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影响因子：
9.9
作者：
Hagemans, MLC;Winkel, LPF;Van der Ploeg, AT
通讯作者：
Van der Ploeg, AT
影响因子：
8.8
作者：
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影响因子：
3.5
作者：
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通讯作者：
Reuser, AJJ
DOI：
10.1007/bf02889851
发表时间：
1984-01-01
期刊：
VIRCHOWS ARCHIV B-CELL PATHOLOGY INCLUDING MOLECULAR PATHOLOGY
影响因子：
--
作者：
GRIFFIN, JL
通讯作者：
GRIFFIN, JL
影响因子：
4.1
作者：
HERS, HG
通讯作者：
HERS, HG