Severe hypomineralisation of the rib cage can lead to fatal respiratory manifestations.1,2

Defective bone mineralisation in hypophosphatasia (HPP) can cause rachitic chest, resulting in decreased thoracic volume and pulmonary hypoplasia.1,3-5

Severe respiratory manifestations of hypophosphatasia range from progressive respiratory insufficiency to respiratory failure3-5
  • Respiratory failure is the most common cause of death in infants with hypophosphatasia1,3

In patients with hypophosphatasia, the need for invasive respiratory support usually results in a fatal outcome.8

Patients with hypophosphatasia with respiratory insufficiency often require intubation, mechanical ventilation, and/or oxygen support.8

In a natural history study of patients ≤5 years of age with hypophosphatasia (N=48)8,b:

64% (29/45) of patients with hypophosphatasia required respiratory support, most commonly invasive ventilation (mechanical ventilation via intubation or tracheostomy)
  • 95% (18/19) of patients who required invasive ventilation died

aRadiographs are from different patients with hypophosphatasia.

bData from a noninterventional, retrospective chart review study designed to understand the natural history of 48 patients with severe perinatal- and infantile-onset hypophosphatasia ≤5 years of age.8

  1. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev. 2013;10(suppl 2):380-388.
  2. Whyte MP. Hypophosphatasia. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. Vol 4. 8th ed. New York, NY: McGraw-Hill; 2001:5313-5329.
  3. Baumgartner-Sigl S, Haberlandt E, Mumm S, et al. Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia caused by two novel missense mutations (c.677T>C, p.M226T; c.1112C>T, p.T371I) of the tissue-nonspecific alkaline phosphatase gene. Bone. 2007;40(6):1655-1661.
  4. Balasubramaniam S, Bowling F, Carpenter K, et al. Perinatal hypophosphatasia presenting as neonatal epileptic encephalopathy with abnormal neurotransmitter metabolism secondary to reduced co-factor pyridoxal-5'-phosphate availability. J Inherit Metab Dis. 2010;33(3):25-33.
  5. Silver MM, Vilos GA, Milne KJ. Pulmonary hypoplasia in neonatal hypophosphatasia. Pediatr Pathol. 1988;8(5):483-493.
  6. Rodriguez E, Bober MB, Davey L, et al. Pediatr Pulmonol. 2012;47(9):917-922.
  7. Simmons JH. Best practices in: recognizing and diagnosing hypophosphatasia. Clinical Endocrinology News website. Published September 30, 2013. Accessed June 8, 2016.
  8. Whyte MP, Leung E, Wilcox W, et al; for Study 011-10 Investigators. Hypophosphatasia: a retrospective natural history study of the severe perinatal and infantile forms. Poster presented at: 2014 Pediatric Academic Societies and Asian Society for Pediatric Research Joint Meeting; May 3-6, 2014; Vancouver, BC.