A case of perinatal hypophosphatasia with a novel mutation in the ALPL gene: Clinical course and review of the literature

Maki Oyachi, Daisuke Harada, Natsuko Sakamoto, Kaoru Ueyama, Kawai Kondo, Kanako Kishimoto, Masafumi Izui, Yuiko Nagamatsu, Hiroko Kashiwagi, Miho Yamamuro, Makoto Tamura, Shin Kikuchi, Tomoyuki Akiyama, Toshimi Michigami, Yoshiki Seino, Noriyuki Namba

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Hypophosphatasia (HPP) is a metabolic bone disease characterized by failure of bone calcification and vitamin B6 dependent seizures. It is caused by loss-of-function mutations in the ALPL gene. A newborn girl required respiratory support by nasal-directional positive airway pressure at birth, and pyridoxine hydrochloride administration for vitamin B6-dependent seizures observed from day two. Umbilical cord blood showed low alkaline phosphatase (ALP) activity and high pyridoxal phosphate levels. Radiographs showed severe rickets-like appearance of the bones. Genetic analysis of the ALPL gene revealed compound heterozygous mutations, c.1559delT/p.Ser188Pro. We diagnosed her with perinatal severe HPP, and started the patient on asfotase alfa from day six. Following enzyme replacement therapy (ERT), skeletal mineralization and respiratory insufficiency improved with no remarkable side-effects. Crying vital capacity (CVC) was used to evaluate respiratory status, which continuously improved from 13.3 mL/kg (day 22) to 20.6 mL/kg (day 113). Since no seizures occurred, pyridoxine hydrochloride was tapered off at one year of age. Strategies to manage perinatal severe HPP cases following ERT have not been established till date. A review of the literature shows that CVC may be a good indicator for weaning from ventilatory support. In addition, ERT will most likely enable withdrawal of pyridoxine treatment.

Original languageEnglish
Pages (from-to)179-186
Number of pages8
Journalclinical pediatric endocrinology
Issue number3
Publication statusPublished - 2018


  • ALPL
  • Asfotase alfa
  • Crying vital capacity
  • Pyridoxal phosphate
  • Pyridoxine hydrochloride

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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