Millán José Luis, Whyte Michael P
Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA.
Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, MO, 63110, USA.
Calcif Tissue Int. 2016 Apr;98(4):398-416. doi: 10.1007/s00223-015-0079-1. Epub 2015 Nov 21.
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.
低磷酸酯酶症（HPP）是由碱性磷酸酶基因（ALPL）突变引起的，导致组织非特异性碱性磷酸酶同工酶（TNAP）活性不足，从而使无机焦磷酸（PPi）在细胞外积聚。PPi是TNAP的天然底物，也是矿化的强效抑制剂。因此，HPP的特征是佝偻病或骨软化症以及牙齿矿化不足。从出生起就使用靶向矿物质的TNAP进行酶替代，可预防TNAP基因敲除小鼠出现严重的HPP，随后证明该方法可挽救并有效治疗患有危及生命的HPP的婴幼儿。临床试验正在揭示HPP病理生理学中尚未完全了解的方面，例如严重HPP时的颅骨缝早闭和肌肉无力。正在开发新的治疗方法以改善患者护理。
