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Calcified Tissue International
Published in: Calcified Tissue International 4/2016

Open Access 01-04-2016 | Review

Alkaline Phosphatase and Hypophosphatasia

Authors: José Luis Millán, Michael P. Whyte

Published in: Calcified Tissue International | Issue 4/2016

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Abstract

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.
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Metadata
Title
Alkaline Phosphatase and Hypophosphatasia
Authors
José Luis Millán
Michael P. Whyte
Publication date
01-04-2016
Publisher
Springer US
Published in
Calcified Tissue International / Issue 4/2016
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-015-0079-1

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