Alkaline Phosphatase and Hypophosphatasia

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.

Keywords: Calcification; Enzyme replacement; Osteomalacia; Rickets; Seizures.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alkaline Phosphatase / deficiency*
  • Alkaline Phosphatase / genetics
  • Animals
  • Humans
  • Hypophosphatasia* / enzymology
  • Hypophosphatasia* / genetics
  • Hypophosphatasia* / therapy
  • Mice


  • ALPL protein, human
  • Alkaline Phosphatase