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

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

Author information

1
Department of Neonatal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, Japan. yyyokoyokooo@ybb.ne.jp.
2
Department of Neonatal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, Japan. kitajima@mch.pref.osaka.jp.
3
Department of Neonatal Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, Japan. narutaka@mch.pref.osaka.jp.
4
Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Japan. tkitaoka@ped.med.osaka-u.ac.jp.
5
Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, Japan. michigami@mch.pref.osaka.jp.
6
Department of Pediatric Nephrology and Metabolism, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka, Japan. michigami@mch.pref.osaka.jp.
7
Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Japan. keioz@ped.med.osaka-u.ac.jp.

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

PMID:
26459154
DOI:
10.1007/s00431-015-2641-2
[Indexed for MEDLINE]

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