Positive maternal serum triple test screening in severe early onset hypophosphatasia.
OBJECTIVE
Hypophosphatasia is a rare heritable inborn error of metabolism characterized by a liver/bone/kidney alkaline phosphatase defective bone mineralization due to mutations in the tissue-non-specific alkaline phosphatase (TNS-ALP) gene. To date 128 mutations are described in the TNS-ALP gene located on the short arm of chromosome 1. The clinical presentation of hypophosphatasia is variable ranging from early onset lethal short-limb dwarfism to a late-onset presentation with fractures in childhood or adulthood.


METHODS
We report a pregnancy with a positive maternal serum triple test screening and a post-mortem pathological and molecular diagnosis of perinatal lethal hypophosphatasia.


RESULTS
Two heterogeneous missense mutations in the TNS-ALP gene were found, of which one was not previously described.


CONCLUSIONS
This case report adds to the list of fetal malformations found after positive maternal serum triple test screening and reports a previously undescribed mutation in the TNS-ALP gene responsible for hypophosphatasia.
Department of Obstetrics and Gynecology, University of Leuven, Leuven, Belgium. Ingrid.Witters@uz.kuleuven.ac.be
Ingrid
I
Witters
Philippe
P
Moerman
Etienne
E
Mornet
Jean-Pierre
JP
Fryns
D000469:Alkaline Phosphatase / Q000172:deficiency / Q000235:genetics*; D000649:Amniocentesis; D002878:Chromosomes, Human, Pair 1; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D005865:Gestational Age; D006801:Humans; D007014:Hypophosphatasia / Q000175:diagnosis* / Q000196:embryology / Q000235:genetics; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D016216:Ultrasonography, Prenatal
D000469:Alkaline Phosphatase