Severe perinatal hypophosphatasia due to homozygous deletion of T at nucleotide 1559 in the tissue nonspecific alkaline phosphatase gene

Objectives Hypophosphatasiais an inherited disorder characterized by defective bone mineralization and deficiency of tissue nonspecific alkaline phosphatase(TNSALP) activity. This disorder is caused by various mutations in the TNSALP gene. We report here hypophosphatasiain two siblings, both of them severely affected by the perinatal (lethal) type. Methods We diagnosed the first infant by clinical and radiologic manifestations, and laboratory findings. Laboratory findings were characterized by deficiency of serum alkaline phosphatase. Both parents and the second infant were then analyzed by molecular techniques. Results The radiograph of the first infant showed severe hypomineralization of the skeleton. Molecular analysis of the second infant showed that this condition was caused by a homozygous single T nucleotide deletion at cDNA number 1559 (1559delT). Both parents were heterozygous carriers for this mutation, although they were not consanguineous. Conclusion This mutation has been frequently found in Japanese hypophosphatasiapatients, but this is the first observation of a homozygous deletion. This report shows that homozygosity for the 1559delT mutation of the TNSALP gene results in a severe lethal phenotype. Copyright © 2003 John Wiley & Sons, Ltd.