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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The authors are grateful to the families who participated in this study and to Sharon Allentuck for administrative assistance.
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Communicated by: Daniela Karall
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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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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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