Lethal hypophosphatasia successfully treated with enzyme replacement from day 1 after birth

Eur J Pediatr. 2016 Mar;175(3):433-7. doi: 10.1007/s00431-015-2641-2. Epub 2015 Oct 12.


Hypophosphatasia (HPP) is a rare metabolic bone disease caused by loss-of-function mutations in the gene ALPL encoding the tissue nonspecific alkaline phosphatase (TNSALP). There is a broad range of severity in the phenotype of HPP, and the most severe form exhibits perinatal lethality without mineralization of the skeleton. Here, we describe a female infant with perinatal lethal HPP diagnosed in utero. She was treated with a recombinant ALP (asfotase alfa) as an enzyme replacement therapy (ERT), which started from 1 day after birth. She required invasive ventilation immediately upon birth and demonstrated severe hypomineralization of whole body bone. Severe respiratory insufficiency was controlled by intensive respiratory care with high-frequency oscillation ventilation and nitric oxide inhalation and deep sedation just after birth. Bone mineralization improved with treatment; improvements were visible by 3 weeks of age and continued with treatment. Serum calcium levels decreased following treatment, resulting in hypocalcemia and convulsion, and calcium supplementation was required until 3 months of treatment. She was weaned from mechanical ventilation and has now survived more than 1 year.

Conclusion: This case demonstrates the success of ERT in treating the severest HPP and highlights the importance of early diagnosis and intervention for these patients.

Keywords: Enzyme replacement therapy; Hypophosphatasia; Pulmonary hypoplasia; Tissue nonspecific alkaline phosphatase.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / adverse effects
  • Alkaline Phosphatase / therapeutic use*
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Calcium / metabolism
  • Enzyme Replacement Therapy / adverse effects
  • Enzyme Replacement Therapy / methods*
  • Female
  • Humans
  • Hypophosphatasia / drug therapy*
  • Immunoglobulin G / adverse effects
  • Immunoglobulin G / therapeutic use*
  • Infant
  • Infant, Newborn
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / therapeutic use*
  • Respiration, Artificial
  • Respiratory Insufficiency / complications*
  • Respiratory Insufficiency / therapy


  • Immunoglobulin G
  • Recombinant Fusion Proteins
  • Alkaline Phosphatase
  • Calcium
  • asfotase alfa

Supplementary concepts

  • Hypophosphatasia, Perinatal Lethal