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Hypophosphatasia (HPP) causes progressive and devastating systemic consequences in patients of all ages.1

As a result of low alkaline phosphatase (ALP) activity and defective bone mineralization, patients may experience a variety of signs and symptoms throughout life.1-4

Dental

  • Premature loss of deciduous or adult teeth1,5,6
  • Abnormal dentition1
  • Periodontal disease7,8
Rachitic chest and hypoplastic lungs are respiratory symptoms of hypophosphatasia

Respiratory

In infants:

  • Pulmonary hypoplasia1,9
  • Respiratory insufficiency1,2,9
  • Need for ventilation support1,10
Fractures and skeletal deformity are skeletal symptoms of hypophosphatasia

Skeletal

  • Hypophosphatasia-induced rickets11,12
  • Skeletal deformities1
  • Osteomalacia13
  • Osteopenia/ osteoporosis1,14
  • Fractures15-17
  • Bone pain1
Craniosynostosis and vitamin B6–responsive seizures are neurologic symptoms of hypophosphatasia

Neurologic

  • Vitamin B6-responsive seizures18
  • Neurologic consequences of craniosynostosis19
Hypercalcemia and hypercalciuria are renal symptoms of hypophosphatasia

Renal

  • Nephrocalcinosis1,20
  • Progressive renal damage21-23
  • Renal failure21

Muscular/Rheumatologic

  • Muscle weakness1,24,25
  • Calcium pyrophosphate dihydrate (CPPD) deposition disease/pseudogout/ chondrocalcinosis1,26,27
  • Muscle and joint pain1,24,28

Symptoms for hypophosphatasia may appear at any age and may worsen over time.1,4,31,32

Learn More

About the progressive nature of hypophosphatasia.

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References:
  1. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev. 2013;10(suppl 2):380-388.
  2. 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.
  3. Whyte MP. Hypophosphatasia: nature’s window on alkaline phosphatase function in humans. In: Bilezikian JP, Raisz LG, Martin TJ, eds. Principles of Bone Biology. Vol 2. 3rd ed. San Diego, CA: Academic Press; 2008:1573-1598.
  4. Weber TJ, Sawyer EK, Moseley S, Odrljin T, Kishnani PS. Burden of disease in adult patients with hypophosphatasia: results from patient-reported outcome surveys. Poster presented at: Endocrine Society Annual Meeting; March 5-8, 2015; San Diego, CA.
  5. Whyte MP, Murphy WA, Fallon MD. Adult hypophosphatasia with chondrocalcinosis and arthropathy. Variable penetrance of hypophosphatasemia in a large Oklahoma kindred. Am J Med. 1982;72(4):631-641.
  6. Reibel A, Maniére M-C, Clauss F, et al. Orodental phenotype and genotype findings in all subtypes of hypophosphatasia. Orphanet J Rare Dis. 2009;4:6.
  7. Foster BL, Ramnitz MS, Gafni RI, et al. Rare bone diseases and their dental, oral, and craniofacial manifestations. J Dent Res. 2014;93(suppl 7):7S-19S.
  8. Watanabe H, Umeda M, Seki T, Ishikawa I. Clinical and laboratory studies of severe periodontal disease in an adolescent associated with hypophosphatasia. A case report. J Periodontol. 1993;64(3):174-180.
  9. Silver MM, Vilos GA, Milne KJ. Pulmonary hypoplasia in neonatal hypophosphatasia. Pediatr Pathol. 1988;8(5):483-493.
  10. 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.
  11. Whyte MP, Greenberg CR, Salman N, et al. N Engl J Med. 2012;366(10):904-913.
  12. Beck C, Morbach H, Wirth C, Beer M, Girschick HJ. Whole-body MRI in the childhood form of hypophosphatasia. Rheumatol Int. 2011;31(10):1315-1320.
  13. Barvencik F, Beil FT, Gebauer M, et al. Skeletal mineralization defects in adult hypophosphatasia--a clinical and histological analysis. Osteoporos Int. 2011;22(10):2667-2675.
  14. Mornet E, Nunes ME. Hypophosphatasia. In: Pagon RA, Adam MP, Ardinger HH, et al, eds. GeneReviews. Seattle, WA: University of Washington, Seattle; 1993. http://www.ncbi.nlm.nih.gov/books/NBK1150/. Published November 20, 2007. Updated February 4, 2016. Accessed October 26, 2017.
  15. Coe JD, Murphy WA, Whyte MP. Management of femoral fractures and pseudofractures in adult hypophosphatasia. J Bone Joint Surg Am. 1986;68(7):981-990.
  16. Gagnon C, Sims NA, Mumm S, et al. Lack of sustained response to teriparatide in a patient with adult hypophosphatasia. J Clin Endocrinol Metab. 2010;95(3):1007-1012.
  17. Schalin-Jäntti C, Mornet E, Lamminen A, Välimäki MJ. Parathyroid hormone treatment improves pain and fracture healing in adult hypophosphatasia. J Clin Endocrinol Metab. 2010;95(12):5174-5179.
  18. 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.
  19. Collmann H, Mornet E, Gattenlöhner S, Beck C, Girschick H. Neurosurgical aspects of childhood hypophosphatasia. Childs Nerv Syst. 2009;25(2):217-223.
  20. Mohn A, De Leonibus C, de Giorgis T, Mornet E, Chiarelli F. Hypophosphatasia in a child with widened anterior fontanelle: lessons learned from late diagnosis and incorrect treatment. Acta Paediatr. 2011;100(7):e43-e46.
  21. Eade AWT, Swannell AJ, Williamson N. Pyrophosphate arthropathy in hypophosphatasia. Ann Rheum Dis. 1981;40(2):164-170.
  22. Whyte MP. Hypophosphatasia. In: Thakker RV, Whyte MP, Eisman JA, Igarashi T, eds. Genetics of Bone Biology and Skeletal Disease. London, UK: Academic Press; 2013:337-360.
  23. Whyte MP, Leelawattana R, Reinus WR, Yang C, Mumm S, Novack DV. Acute severe hypercalcemia after traumatic fractures and immobilization in hypophosphatasia complicated by chronic renal failure. J Clin Endocrinol Metab. 2013;98(12):4606-4612.
  24. Seshia SS, Derbyshire G, Haworth JC, Hoogstraten J. Myopathy with hypophosphatasia. Arch Dis Child. 1990;65(1):130-131.
  25. Data on file, Alexion Pharmaceuticals.
  26. Chuck AJ, Pattrick MG, Hamilton E, Wilson R, Doherty M. Crystal deposition in hypophosphatasia: a reappraisal. Ann Rheum Dis. 1989;48(7):571-576.
  27. Whyte MP. Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann N Y Acad Sci. 2010;1192:190-200.
  28. Whyte MP, Madson KL, Munns CF, et al. A retrospective, multi-national, non-interventional, natural history study of the childhood form of hypophosphatasia [abstract LB-OR01]. Endocrine Society’s 97th Annual Meeting and Expo website. https://endo.confex.com/endo/2015endo/webprogram/Paper22822.html. Accessed October 26, 2017.
  29. Taketani T, Onigata K, Kobayashi H, Mushimoto Y, Fukuda S, Yamaguchi S. Clinical and genetic aspects of hypophosphatasia in Japanese patients. Arch Dis Child. 2014;99(3):211-215.
  30. Simmons JH. Best practices in: recognizing and diagnosing hypophosphatasia. Clinical Endocrinology News website. http://www.mdedge.com/sites/default/files/issues/articles/Alexion_10_11_Final_Web.pdf. Published September 30, 2013. Accessed October 26, 2017.
  31. Caswell AM, Whyte MP, Russell RG. Hypophosphatasia and the extracellular metabolism of inorganic pyrophosphate: clinical and laboratory aspects. Crit Rev Clin Lab Sci. 1991;28(3):175-232.
  32. Birtwell WM Jr, Riggs BL, Peterson LFA, Jones JD. Hypophosphatasia in an adult. Arch Intern Med. 1967;120(1):90-93.