title: Lethal hypophosphatasia successfully treated with enzyme replacement from day 1 after birth.
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.
  
  
  CONCLUSIONS
  This case demonstrates the success of ERT in treating the severest HPP and highlights the importance of early diagnosis and intervention for these patients.
authors.affiliation: 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.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Okazaki
authors.affiliation: 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.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitajima
authors.affiliation: 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.
authors.forename: Narutaka
authors.initials: N
authors.lastname: Mochizuki
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Japan. tkitaoka@ped.med.osaka-u.ac.jp.
authors.forename: Taichi
authors.initials: T
authors.lastname: Kitaoka
authors.affiliation: 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.|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.
authors.forename: Toshimi
authors.initials: T
authors.lastname: Michigami
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, Japan. keioz@ped.med.osaka-u.ac.jp.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
mesh_terms: D000469:Alkaline Phosphatase / Q000009:adverse effects / Q000627:therapeutic use*; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D056947:Enzyme Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D007014:Hypophosphatasia / Q000188:drug therapy*; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D012121:Respiration, Artificial; D012131:Respiratory Insufficiency / Q000150:complications* / Q000628:therapy
chemical_list: D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D000469:Alkaline Phosphatase; D002118:Calcium; C570710:asfotase alfa
keywords: Enzyme replacement therapy; Hypophosphatasia; Pulmonary hypoplasia; Tissue nonspecific alkaline phosphatase