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Outcome of Perinatal Hypophosphatasia in Manitoba Mennonites: A Retrospective Cohort Analysis

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JIMD Reports - Volume 11

Part of the book series: JIMD Reports ((JIMD,volume 11))

Abstract

Hypophosphatasia (HPP) is the metabolic bone disease caused by loss-of-function mutation within the gene that encodes the “tissue nonspecific” isoenzyme of alkaline phosphatase (TNSALP). Perinatal HPP is usually fatal due to respiratory insufficiency, and infantile HPP often has a similar outcome although no formal study into the natural history of these severe forms of HPP has been undertaken. We reviewed our 80-year (1927–2007) cohort of 15 Canadian patients with perinatal HPP. All had Mennonite heritage. Family linkage studies indicated that nine were homozygous for a TNSALP disease allele, likely Gly334Asp. Three patients had parents who were carriers for the Gly334Asp allele by mutation analysis. One patient was confirmed by mutation analysis to be homozygous for the TNSALP Gly334Asp mutation. One patient who had only one Mennonite parent was a genetic compound for the Gly334Asp mutation and the Val382Ile mutation. This patient’s sibling was also affected. All 15 patients had profound skeletal hypomineralization, severe rickets, and respiratory insufficiency. All died by 9 months of age, usually soon after birth, from pulmonary failure.

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Acknowledgments

The authors are grateful to the families who participated in this study and to Sharon Allentuck for administrative assistance.

Author information

Authors and Affiliations

  1. Manitoba Institute of Child Health and Department of Pediatrics and Child Health, University of Manitoba, AE308 – 820 Sherbrook St, R3A 1R9, Winnipeg, Manitoba, Canada

    Edward C. W. Leung, Aizeddin A. Mhanni, Martin Reed & Cheryl R. Greenberg

  2. Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children and Division of Bone and Mineral Diseases, Washington University School of Medicine, St. Louis, MO, USA

    Michael P. Whyte

  3. Alexion Pharmaceuticals, Chesire, CT, USA

    Hal Landy

Authors
  1. Edward C. W. Leung
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  2. Aizeddin A. Mhanni
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  3. Martin Reed
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  4. Michael P. Whyte
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  5. Hal Landy
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  6. Cheryl R. Greenberg
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Corresponding author

Correspondence to Edward C. W. Leung .

Editor information

Editors and Affiliations

  1. Medizinische Universität Innsbruck Sektionen für Humangenetik und Klinische, Innsbruck, Austria

    Johannes Zschocke

  2. Clinical Pharmacology Unit, Division of Health Sciences Washington State University, Spokane, Washington, USA

    K Michael Gibson

  3. Department of Biochemistry Genetics Unit, University of Oxford, Oxford, United Kingdom

    Garry Brown

  4. Department of Pediatrics IGMD, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands

    Eva Morava

  5. Center for Child and Adolescent Medicine Heidelberg University Hospital, Heidelberg, Germany

    Verena Peters

Additional information

Communicated by: Daniela Karall

Appendices

Competing Interest

Dr. Edward C.W. Leung received a research stipend and research grant support from Alexion Pharmaceuticals. Dr. Cheryl Greenberg received research grant support from Alexion Pharmaceuticals. Dr. Michael P. Whyte received consulting fees and research grant support from Alexion Pharmaceuticals.

Synopsis

Perinatal hypophosphatasia in Manitoba Mennonites has been uniformly fatal.

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© 2013 SSIEM and Springer-Verlag Berlin Heidelberg

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Leung, E.C.W., Mhanni, A.A., Reed, M., Whyte, M.P., Landy, H., Greenberg, C.R. (2013). Outcome of Perinatal Hypophosphatasia in Manitoba Mennonites: A Retrospective Cohort Analysis. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Volume 11. JIMD Reports, vol 11. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2013_224

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  • DOI: https://doi.org/10.1007/8904_2013_224

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-37327-5

  • Online ISBN: 978-3-642-37328-2

  • eBook Packages: MedicineMedicine (R0)

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