Fighting HPP Every Day

What is hypophosphatasia (HPP)?

HPP is a genetic, chronic, progressive, and life-threatening metabolic disease in which patients experience devastating effects on multiple systems of the body, leading to debilitating or life-threatening complications.1 HPP is characterized by low alkaline phosphatase (ALP) activity and defective bone mineralization that can lead to destruction and deformity of bones and other skeletal abnormalities, as well as systemic complications such as muscle weakness and respiratory failure leading to premature death in infants.1-3

Evie, diagnosed with HPP at 2 weeks old, playing on a playground

HPP is caused by a defect (mutation) in the gene that makes an enzyme known as tissue nonspecific alkaline phosphatase (TNSALP), resulting in low levels of ALP activity.1,4,5

When ALP is functioning normally, it allows 2 key minerals—calcium and phosphate—to bind together to form healthy, mineralized bones.4,6 In patients with HPP, however, ALP activity is low, leading to insufficient mineralization of bone and altered calcium and phosphate metabolism.7

Many patients with HPP have weak, soft, or brittle bones, as well as skeletal deformities, including HPP-related rickets and bowed legs.1-3,7 These abnormalities can impede growth in children and can continue to impair a person’s mobility.8,9

Infants and young children may experience severe symptoms of HPP, such as respiratory failure, that can lead to premature death or severe breathing complications that require an assistive breathing device.1,9 In a retrospective natural history study of children with severe HPP, those who experienced their first symptom of HPP prior to 6 months of age had a very high mortality rate—73% at 5 years.9

Symptom locations of HPP on the human body

Symptoms of HPP3-7

  • Low alkaline phosphatase (ALP) activity
  • Reduced bone mineralization
  • Muscle weakness
  • Respiratory failure due to rachitic chest, leading to premature death in infants
  • Fractures and skeletal abnormalities
  • Bone/joint/muscle pain
  • Developmental delays/impaired mobility


  1. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev. 2013;10(suppl 2):380-388.
  2. Fraser D. Hypophosphatasia. Am J Med. 1957;22(5):730-746.
  3. Whyte MP, Greenberg CR, Salman N, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012;366(10):904-913.
  4. 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 1. 3rd ed. San Diego, CA: Academic Press; 2008:1573-1598.
  5. 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.
  6. Whyte MP. Physiological role of alkaline phosphatase explored in hypophosphatasia. Ann N Y Acad Sci. 2010;1192:190-200.
  7. Beck C, Morbach H, Stenzel M, et al. Hypophosphatasia: recent advances in diagnosis and treatment. Open Bone J. 2009;1:8-15.
  8. Seshia SS, Derbyshire G, Haworth JC, et al. Myopathy with hypophosphatasia. Arch Dis Child. 1990;65(1):130-131.
  9. Whyte MP, Leung E, Wilcox W, et al. Hypophosphatasia: a retrospective natural history study of the severe perinatal and infantile forms. Poster presented at the 2014 Pediatric Academic Societies and Asian Society for Pediatric Research Joint Meeting, Vancouver, B.C., Canada, May 5, 2014. Abstract 752416.

Tanner, diagnosed with HPP at 4 days old, with a stuffed animal
My hope for Tanner in the future is that he enters into adulthood. I kind of hope that he will be a doctor, and maybe help kids like doctors have helped him.”