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

  • Edward C. W. LeungEmail author
  • Aizeddin A. Mhanni
  • Martin Reed
  • Michael P. Whyte
  • Hal Landy
  • Cheryl R. Greenberg
Research Report
Part of the JIMD Reports book series (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.

Keywords

Enzyme Replacement Therapy Founder Mutation Head Circumference Measurement Gly334Asp Mutation Manitoba Health Research 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

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

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Edward C. W. Leung
    • 1
    Email author
  • Aizeddin A. Mhanni
    • 1
  • Martin Reed
    • 1
  • Michael P. Whyte
    • 2
  • Hal Landy
    • 3
  • Cheryl R. Greenberg
    • 1
  1. 1.Manitoba Institute of Child Health and Department of Pediatrics and Child HealthUniversity of ManitobaWinnipegCanada
  2. 2.Center for Metabolic Bone Disease and Molecular Research, Shriners Hospital for Children and Division of Bone and Mineral DiseasesWashington University School of MedicineSt. LouisUSA
  3. 3.Alexion PharmaceuticalsChesireUSA

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