Alkaline Phosphatase and Hypophosphatasia

José Luis Millán, Michael P. Whyte

Research output: Contribution to journalReview article

125 Scopus citations

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.

Original languageEnglish
Pages (from-to)398-416
Number of pages19
JournalCalcified Tissue International
Volume98
Issue number4
DOIs
StatePublished - Apr 1 2016

Keywords

  • Calcification
  • Enzyme replacement
  • Osteomalacia
  • Rickets
  • Seizures

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