Alkaline Phosphatase and Hypophosphatasia.
Alkaline Phosphatase and Hypophosphatasia.
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DOI：
10.1007/s00223-015-0079-1
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发表时间：
2016-04
影响因子：
4.2
通讯作者：
Whyte MP
中科院分区：
文献类型：
--
作者：
Millán JL;Whyte MP
低磷酸症（HPP）是由于ALPL突变导致组织非特异性碱性磷酸酶同工酶（TNAP）活性不足，从而导致细胞外无机焦磷酸盐（PPi）的积累，无机焦磷酸盐是TNAP的天然底物和矿化的有效抑制剂。因此，HPP以牙齿佝偻病或骨软化和低矿化为特征。在TNAP基因敲除的小鼠中，从出生开始使用矿物质靶向TNAP进行酶替代，可预防严重的HPP，随后被证明可挽救并有效治疗危及生命的HPP婴儿和幼儿。临床试验揭示了HPP病理生理学尚未完全了解的方面，如HPP严重时的颅缝闭锁和肌肉无力。正在开发新的治疗方法以改善患者护理。
Hypophosphatasia (HPP) results from ALPL mutations leading to deficient activity of the tissue-non-specific alkaline phosphatase isozyme (TNAP) and thereby extracellular accumulation of inorganic pyrophosphate (PPi), a natural substrate of TNAP and potent inhibitor of mineralization. Thus, HPP features rickets or osteomalacia and hypomineralization of teeth. Enzyme replacement using mineral-targeted TNAP from birth prevented severe HPP in TNAP-knockout mice and was then shown to rescue and substantially treat infants and young children with life-threatening HPP. Clinical trials are revealing aspects of HPP pathophysiology not yet fully understood, such as craniosynostosis and muscle weakness when HPP is severe. New treatment approaches are under development to improve patient care.