Alkaline Phosphatase and Hypophosphatasia

José Luis Millán; Michael P. Whyte

doi:10.1007/s00223-015-0079-1

Alkaline Phosphatase and Hypophosphatasia

José Luis Millán, Michael P. Whyte

Research output: Contribution to journal › Review article › peer-review

301 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 (PP_i), 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 language	English
Pages (from-to)	398-416
Number of pages	19
Journal	Calcified Tissue International
Volume	98
Issue number	4
DOIs	https://doi.org/10.1007/s00223-015-0079-1
State	Published - Apr 1 2016

Keywords

Calcification
Enzyme replacement
Osteomalacia
Rickets
Seizures

Access to Document

10.1007/s00223-015-0079-1

Cite this

@article{fa1a9fb6c17a4d3cb1ce4efc21e0e1a7,

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.",

keywords = "Calcification, Enzyme replacement, Osteomalacia, Rickets, Seizures",

author = "Mill{\'a}n, {Jos{\'e} Luis} and Whyte, {Michael P.}",

note = "Publisher Copyright: {\textcopyright} 2015, The Author(s).",

year = "2016",

month = apr,

day = "1",

doi = "10.1007/s00223-015-0079-1",

language = "English",

volume = "98",

pages = "398--416",

journal = "Calcified Tissue International",

issn = "0171-967X",

number = "4",

}

TY - JOUR

T1 - Alkaline Phosphatase and Hypophosphatasia

AU - Millán, José Luis

AU - Whyte, Michael P.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - 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.

AB - 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.

KW - Calcification

KW - Enzyme replacement

KW - Osteomalacia

KW - Rickets

KW - Seizures

UR - http://www.scopus.com/inward/record.url?scp=84947750321&partnerID=8YFLogxK

U2 - 10.1007/s00223-015-0079-1

DO - 10.1007/s00223-015-0079-1

M3 - Review article

C2 - 26590809

AN - SCOPUS:84947750321

SN - 0171-967X

VL - 98

SP - 398

EP - 416

JO - Calcified Tissue International

JF - Calcified Tissue International

IS - 4

ER -

Alkaline Phosphatase and Hypophosphatasia

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this