Natural History of Perinatal and Infantile Hypophosphatasia: A Retrospective Study

Study 011-10 Investigators

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21 Scopus citations


Objective: To report clinical characteristics and medical history data obtained retrospectively for a large cohort of pediatric patients with perinatal and infantile hypophosphatasia. Study design: Medical records from academic medical centers known to diagnose and/or treat hypophosphatasia were reviewed. Patients born between 1970 and 2011 with hypophosphatasia and any of the following signs/symptoms at age <6 months were eligible: vitamin B6–dependent seizures, respiratory compromise, or rachitic chest deformity (NCT01419028). Patient demographics and characteristics, respiratory support requirements, invasive ventilator–free survival, and further complications of hypophosphatasia were followed for up to the first 5 years of life. Results: Forty-eight patients represented 12 study sites in 7 countries; 13 patients were alive, and 35 were dead (including 1 stillborn). Chest deformity, respiratory distress, respiratory failure (as conditioned by the eligibility criteria), failure to thrive, and elevated calcium levels were present in >70% of patients between birth and age 5 years. Vitamin B6–dependent seizures and respiratory distress and failure were associated significantly (P <.05)with the risk of early death. Serum alkaline phosphatase activity in all 41 patients tested (mean [SD]: 18.1 [15.4]U/L)was below the mean lower limit of normal of the reference ranges of the various laboratories (88.2 U/L). Among the 45 patients with relevant data, 29 had received respiratory support, of whom 26 had died at the time of data collection. The likelihood of invasive ventilator–free survival for this cohort decreased to 63% at 3 months, 54% at 6 months, 31% at 12 months, and 25% at 5 years. Conclusions: Patients with perinatal or infantile hypophosphatasia and vitamin B6–dependent seizures, with or without significant respiratory distress or chest deformities, have high morbidity and mortality in the first 5 years of life. Trial registration: NCT01419028.

Original languageEnglish
Pages (from-to)116-124.e4
JournalJournal of Pediatrics
StatePublished - Jun 2019


  • alkaline phosphatase
  • craniosynostosis
  • invasive ventilation
  • metabolic bone disease
  • rickets
  • survival


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