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

Objectives: 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.

Conclusion: 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.