title: Alkaline Phosphatase and Hypophosphatasia.
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.
authors.affiliation: Sanford Children's Health Research Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, 92037, USA. millan@burnham.org.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Millán
authors.affiliation: Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children, St. Louis, MO, 63110, USA.|Division of Bone and Mineral Diseases, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO, 63110, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Whyte
mesh_terms: D000469:Alkaline Phosphatase / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D006801:Humans; D007014:Hypophosphatasia / Q000201:enzymology / Q000235:genetics / Q000628:therapy; D051379:Mice
chemical_list: C548267:ALPL protein, human; D000469:Alkaline Phosphatase
keywords: Calcification; Enzyme replacement; Osteomalacia; Rickets; Seizures