Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Perinatal hypophosphatasia: diagnosis and detection of heterozygote carriers within the family

Perinatal hypophosphatasia: diagnosis and detection of heterozygote carriers within the family We report on two families in which one or two children had a severe disorder of skeletal development detected by prenatal ultrasonography. The children died postnatally and showed typical radiological and biochemical findings of perinatal hypophosphatasia. Biochemical analysis revealed a low activity of alkaline phosphatase (AP) and a high value of pyridoxal-5-phosphate (PLP), one of its natural substrates. The screening for mutations of the tissue nonspecific alkaline phosphatase (TNSALP) gene showed homozygosity for a point mutation (G 317→D) in the two affected children of the first family. The affected child of the second family was homozygous for a nonsense mutation (R 411→X). Family screening revealed that the determination of AP and PLP is helpful for detection of heterozygotes. However, heterozygote children had values of AP in the lower normal range during phases of rapid growth. The determination of PLP proved to be more sensitive in these cases. It should be kept in mind that during the last trimester of gestation there is an increase in maternal AP activity and a normalization of PLP due to placental AP, which is not affected. Therefore, in the course of a prenatal diagnosis in an index case, paternal blood should be analyzed in parallel. For detailed genetic counseling and early prenatal diagnosis in following pregnancies, the possibility of mutation analysis should be used. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Genetics Wiley

Perinatal hypophosphatasia: diagnosis and detection of heterozygote carriers within the family

Loading next page...
 
/lp/wiley/perinatal-hypophosphatasia-diagnosis-and-detection-of-heterozygote-oB40nyyPFH

References (22)

Publisher
Wiley
Copyright
Munksgaard 1999
ISSN
0009-9163
eISSN
1399-0004
DOI
10.1034/j.1399-0004.1999.560409.x
Publisher site
See Article on Publisher Site

Abstract

We report on two families in which one or two children had a severe disorder of skeletal development detected by prenatal ultrasonography. The children died postnatally and showed typical radiological and biochemical findings of perinatal hypophosphatasia. Biochemical analysis revealed a low activity of alkaline phosphatase (AP) and a high value of pyridoxal-5-phosphate (PLP), one of its natural substrates. The screening for mutations of the tissue nonspecific alkaline phosphatase (TNSALP) gene showed homozygosity for a point mutation (G 317→D) in the two affected children of the first family. The affected child of the second family was homozygous for a nonsense mutation (R 411→X). Family screening revealed that the determination of AP and PLP is helpful for detection of heterozygotes. However, heterozygote children had values of AP in the lower normal range during phases of rapid growth. The determination of PLP proved to be more sensitive in these cases. It should be kept in mind that during the last trimester of gestation there is an increase in maternal AP activity and a normalization of PLP due to placental AP, which is not affected. Therefore, in the course of a prenatal diagnosis in an index case, paternal blood should be analyzed in parallel. For detailed genetic counseling and early prenatal diagnosis in following pregnancies, the possibility of mutation analysis should be used.

Journal

Clinical GeneticsWiley

Published: Oct 1, 1999

Keywords: alkaline phosphatase; diagnosis; heterozygote carrier; mutation; perinatal hypophosphatasia

There are no references for this article.