Hypophosphatasia

Hypophosphatasia (HPP) is characterized by defective bone mineralization that can lead to deformity of bones and other skeletal abnormalities, as well as systemic complications such as profound muscle weakness, seizures, pain, and respiratory failure leading to premature death in infants.1,2,3 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.4,5

HPP is caused by a defect (mutation) in the gene that makes an enzyme known as tissue non-specific alkaline phosphatase (TNSALP), resulting in low levels of ALP activity.1,6,7 When ALP is functioning normally, it allows two key minerals – calcium and phosphate – to bind together to form healthy, mineralized bones.6,7 In patients with HPP, however, ALP activity is low, leading to insufficient mineralisation of bone and altered calcium and phosphate metabolism which can damage the kidneys, muscles, and joints.8

HPP can affect males and females of all ages and can have devastating outcomes at any stage of life.1 Newborns and children, in particular, may experience severe symptoms of HPP such as seizures and respiratory failure.1 Historically, infants who experienced their first symptom of HPP within the first six months of life had a very high mortality rate — 73 percent at five years.9

Since HPP shares symptoms with other, more common diseases, diagnostic delays and misdiagnoses are common.1,10 However, getting a diagnosis for HPP can be straightforward through a combination of full clinical assessment and a simple blood test for age- and gender-adjusted low ALP activity.1,11 It is critical to get an accurate diagnosis as early as possible to ensure that appropriate care is provided.1,11

For more information on HPP, visit www.HPPsource.eu.

References
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. Seshia SS, Derbyshire G, Haworth JC, Hoogstraten J. Myopathy with hypophosphatasia. Arch Dis Child. 1990;65(1):130-131.
5. Weber, T et al. Burden of Disease in Adult Patients with Hypophosphatasia: Results from Patient-Reported Outcomes Surveys. Poster presented at the Endocrine Society Annual Meeting, San Diego, March 5-8, 2015.
6. 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.
7. 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.
8. 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.
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. 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.
11. Mornet E, Nunes ME. Hypophosphatasia. In: Pagon RA, Bird TD, Dolan CR, Stephen K, eds. GeneReviews. Seattle, WA: University of Washington, Seattle; 1993.