Hypophosphatasia (HPP) is a genetic, chronic and progressive ultra-rare metabolic disease in which patients experience devastating effects on multiple systems of the body, leading to debilitating or life-threatening complications and growth development in children.1,2
HPP is inherited, resulting from a defect (mutation) in the gene that makes an enzyme known as tissue non-specific alkaline phosphatase (TNSALP). The result is low levels of alkaline phosphatase (ALP) activity.1,2 When ALP is functioning normally, it allows two key minerals — calcium and phosphate — to bind together to form healthy, mineralized bones.1,2,3 In patients with HPP, however, ALP activity is low, leading to improper mineralization of bone-building calcium and phosphate.4 Instead, calcium and phosphate can build up in other places throughout the body, causing damage to bones and organs.4
The genetic deficiency in HPP can affect people of all ages, and the disease can have devastating consequences at any stage of life.1 Many patients with HPP have weak or soft bones, leading to frequent fractures, as well as skeletal deformities.1,5,6 These abnormalities can impede growth in children and can continue to impair a person’s ability to engage in routine daily activities such as walking, running, jumping, standing, and climbing stairs.7,8
Infants and young children may experience severe symptoms of HPP.1 In a study following patients not treated with Strensiq, infants who had their first symptom of HPP within the first 6 months of life had high mortality, with an overall mortality rate of 73% at 5 years.9 In these patients, mortality is primarily due to respiratory failure.1,10,11 In patients surviving to adolescence and adulthood, long-term clinical complications include growth retardation, recurrent and non-healing fractures, profound muscle weakness, debilitating pain and the requirement for ambulatory assistive devices such as wheelchairs, wheeled walkers and canes.1,7
Since HPP shares symptoms with other, more common diseases, diagnostic delays and misdiagnoses are common.1,12  However, getting a diagnosis for HPP can be straightforward through a combination of full clinical assessment and a simple blood test for low ALP activity.1,13 It is critical to get an accurate diagnosis as early as possible to ensure that appropriate care is provided.1, 13
1. Rockman-Greenberg C. Hypophosphatasia. Pediatr Endocrinol Rev. 2013; 10(suppl 2):380-388.
2. 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.
3. 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.
4. Beck C, Morbach H, Stenzel M, Collmann H, Schneider P, Girschick HJ. Hypophosphatasia — recent advances in diagnosis and treatment. Open Bone J. 2009;1:8-15.
5. Whyte MP, Greenberg CR, Salman N, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012; 366(10):904-913.
6. Fraser D. Hypophosphatasia. Am J Med. 1957;22(5):730-746.
7. Seshia SS, Derbyshire G, Haworth JC, Hoogstraten J. Myopathy with hypophosphatasia. Arch Dis Child. 1990; 65(1):130-131.
8. Data on file, Alexion Pharmaceuticals.
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.
10. 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.
11. Whyte MP, Rockman-Greenberg C, Hofmann C, et al. Improved survival with asfotase alfa treatment in pediatric patients with hypophosphatasia at high risk of death. Poster presented at the American Society for Bone and Mineral Research (ASBMR) 2014 Annual Meeting, Houston, September 14, 2014. Abstract 1097.
12. 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.
13. Mornet E, Nunes ME. Hypophosphatasia. In: Pagon RA, Bird TD, Dolan CR, Stephen K, eds. GeneReviews. Seattle, WA: University of Washington, Seattle; 1993.