Outcome of perinatal hypophosphatasia in manitoba mennonites: A retrospective cohort analysis

Edward C.W. Leung, Aizeddin A. Mhanni, Martin Reed, Michael P. Whyte, Hal Landy, Cheryl R. Greenberg

Research output: Chapter in Book/Report/Conference proceedingChapter

36 Scopus citations

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.

Original languageEnglish
Title of host publicationJIMD Reports
PublisherSpringer
Pages73-78
Number of pages6
DOIs
StatePublished - Jan 1 2013

Publication series

NameJIMD Reports
Volume11
ISSN (Print)2192-8304
ISSN (Electronic)2192-8312

Keywords

  • Enzyme replacement therapy
  • Founder mutation
  • GLY334ASP mutation
  • Head circumference measurement
  • Manitoba health research

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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 JIMD Reports (pp. 73-78). (JIMD Reports; Vol. 11). Springer. https://doi.org/10.1007/8904_2013_224