Ultrasound Diagnosis of Perinatal Lethal Hypophosphatasia, Confirmed with Targeted Next Generation Sequencing and Identification of a Novel Mutation in ALPL Gene

Author(s): Allybocus Zubair Akbar

Perinatal lethal hypophosphatasia (p-HPP) is a lethal subtype of hypophosphatasia that prioritizes an early detection for appropriate treatment plan. Residual activity of alkaline phosphatase, owing to loss-of-function mutation of ALPL gene, accounts for degree of severity in phenotypes. We present a case of p-HPP in a Chinese couple’s fetus diagnosed at 18 weeks of gestation. Sonographic evaluation revealed a fetus with shortened and deformed limbs and hypoechogenic skull and vertebrae. After p-HPP was clinically diagnosed, the parents opted for medical termination of pregnancy. Further molecular investigation using next generation sequencing revealed the fetus to harbor a compound heterozygous mutation c935_943delTGGTGGTGG (pV313delVVV) and c406C>T (pR136C) in the ALPL gene. The mutation c935_943delTGGTGGTGG (pV313delVVV), of paternal origin, is to the best of our knowledge a novel mutation not reported before. This case demonstrates the importance of ultrasonography and molecular genetic testing in prenatal diagnosis.