Positive maternal serum triple test screening in severe early onset hypophosphatasia.

Abstract

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. We report a pregnancy with a positive maternal serum triple test screening and a post-mortem pathological and molecular diagnosis of perinatal lethal hypophosphatasia. Two heterogeneous missense mutations in the TNS-ALP gene were found, of which one was not previously described. 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.