2. Academic Validation
  3. Lethal hypophosphatasia successfully treated with enzyme replacement from day 1 after birth

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.
Yoko Okazaki 1,  Hiroyuki Kitajima 2,  Narutaka Mochizuki 3,  Taichi Kitaoka 4,  Toshimi Michigami 5 6,  Keiichi Ozono 7
Affiliations

Affiliations

  • 1 Department of Neonatal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, Japan. [email protected].
  • 2 Department of Neonatal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, Japan. [email protected].
  • 3 Department of Neonatal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, Japan. [email protected].
  • 4 Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Japan. [email protected].
  • 5 Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, Japan. [email protected].
  • 6 Department of Pediatric Nephrology and Metabolism, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, Japan. [email protected].
  • 7 Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Japan. [email protected].
PMID: 26459154 DOI: 10.1007/s00431-015-2641-2
Abstract

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.

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