TY - CHAP
T1 - Outcome of perinatal hypophosphatasia in manitoba mennonites
T2 - A retrospective cohort analysis
AU - Leung, Edward C.W.
AU - Mhanni, Aizeddin A.
AU - Reed, Martin
AU - Whyte, Michael P.
AU - Landy, Hal
AU - Greenberg, Cheryl R.
N1 - Funding Information:
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.
Publisher Copyright:
© 2013, SSIEM and Springer-Verlag Berlin Heidelberg.
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
KW - Enzyme replacement therapy
KW - Founder mutation
KW - GLY334ASP mutation
KW - Head circumference measurement
KW - Manitoba health research
UR - http://www.scopus.com/inward/record.url?scp=84954377286&partnerID=8YFLogxK
U2 - 10.1007/8904_2013_224
DO - 10.1007/8904_2013_224
M3 - Chapter
C2 - 23580367
AN - SCOPUS:84954377286
T3 - JIMD Reports
SP - 73
EP - 78
BT - JIMD Reports
PB - Springer
ER -