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Hypophosphatasia: Canadian update on diagnosis and management

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A Correction to this article was published on 29 May 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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  • 29 May 2019

    In the article mentioned above an author’s name was misspelled.

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Acknowledgements

The authors greatly appreciated the support of Hajar Abu Alrob Health Research Methodology, McMaster University for completing the literature search.

Funding

Funding was received from the Canadian Endocrine Update, McMaster University, and Western University.

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Authors and Affiliations

  1. McMaster University, 1280 Main St W, Hamilton, ON, L8S 4L8, Canada

    A.A. Khan

  2. St. Michael’s Hospital and University of Toronto , Toronto, Canada

    R. Josse

  3. Hospital for Sick Kids , Toronto, Canada

    P. Kannu

  4. Le Centre Hospitalier Universitaire de Quebec, Quebec, Canada

    J. Villeneuve

  5. St. Joseph’s Health Care London, London, Ontario, Canada

    T. Paul

  6. Western University, London, Canada

    S. Van Uum

  7. Health Sciences Centre Winnipeg, Winnipeg, Canada

    C.R. Greenberg

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Correspondence to A.A. Khan.

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Conflicts of interests

AK, research funds from Shire, Alexion, and Amgen. RJ, grants/research support: Amgen, AZ, Lilly, speakers Bureau/Honoraria: Amgen, Lilly, Merck, NovoNordisk, advisory board member: Amgen, Merck, Janssen, AZ, Lilly/BI. PK, Alexion honorariums. JV, scientific comity: Amgen and Eli Lilly, Speaker: Amgen and Eli Lilly. TP, no disclosures. SVU, relationships with for-profit and not-for-profit interests; grants/research support: Novartis, Sanofi, speakers Bureau/Honoraria: Abbott, Acerus pharmaceuticals, Novartis, Ipsen, Sanofi, Consulting Fees: Pfizer, other: annual speaker for Addison society. CRG was the Canadian site investigator during the industry-sponsored asfotase alfa clinical trials for which she received grant support from Alexion Pharmaceuticals, Inc. as well as consultancy fees and honoraria for select presentations.

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The original version of this article was revised: In the article mentioned above an author’s name was misspelled. The correct author name reads as follows: S. Van Uum

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Khan, A., Josse, R., Kannu, P. et al. Hypophosphatasia: Canadian update on diagnosis and management. Osteoporos Int 30, 1713–1722 (2019). https://doi.org/10.1007/s00198-019-04921-y

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