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Osteoporosis International

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26.03.2019 | Consensus Statement

Hypophosphatasia: Canadian update on diagnosis and management

verfasst von: A.A. Khan, R. Josse, P. Kannu, J. Villeneuve, T. Paul, S. Van Uum, C.R. Greenberg

Erschienen in: Osteoporosis International | Ausgabe 9/2019

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Abstract

Summary

Hypophosphatasia (HPP) is a rare inherited disorder of bone and mineral metabolism caused by loss of function mutations in the ALPL gene. The presentation in children and adults can be extremely variable and natural history is poorly understood particularly in adults. Careful patient evaluation is required with consideration of pharmacologic intervention in individuals meeting criteria for therapy.

Introduction

The purposes of this review are to present current evidence regarding the diagnosis and management of hypophosphatasia in children and adults and provide evidence-based recommendations for management.

Method

A MEDLINE, EMBASE, and Cochrane database search and literature review was completed. The following consensus recommendations were developed based on the highest level of evidence as well as expert opinion.

Results

Hypophosphatasia is a rare inherited disorder of bone and mineral metabolism due to loss of function mutations in the tissue non-specific alkaline phosphatase (ALPL) gene causing reductions in the activity of the tissue non-specific isoenzyme of alkaline phosphatase (TNSALP). Deficient levels of alkaline phosphatase result in elevation of inhibitors of mineralization of the skeleton and teeth, principally inorganic pyrophosphate. The impaired skeletal mineralization may result in elevations in serum calcium and phosphate. Clinical features include premature loss of teeth, metatarsal and subtrochanteric fractures as well as fragility fractures. Poor bone healing post fracture has been observed. Myalgias and muscle weakness may also be present. In infancy and childhood, respiratory and neurologic complications can occur.

Conclusions

HPP is associated with significant morbidity and mortality. Pharmacologic intervention can result in significant clinical improvement. This Canadian position paper provides an overview of the musculoskeletal, renal, dental, respiratory, and neurologic manifestations of hypophosphatasia. The current state of the art in the diagnosis and management of hypophosphatasia is presented.

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Titel: Hypophosphatasia: Canadian update on diagnosis and management
verfasst von: A.A. Khan
R. Josse
P. Kannu
J. Villeneuve
T. Paul
S. Van Uum
C.R. Greenberg
Publikationsdatum: 26.03.2019
Verlag: Springer London
Erschienen in: Osteoporosis International / Ausgabe 9/2019
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-019-04921-y

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Hypophosphatasia: Canadian update on diagnosis and management

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Introduction

Method

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Conclusions

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