Current Approaches in Management of Patients with Hypophosphatasia

he authors present the latest data on the hypophosphatasia (HPP) management in children. Hypophosphatasia is a rare genetic disease caused by deficiency of tissue-specific alkaline phosphatase due to mutation in the ALPL gene. The article covers all the features of epidemiology, etiology and pathogenesis, detailed stages of differential diagnostics. Treatment guidelines for pediatric patients are provided, they are based on the principles of evidence-based medicine. Special attention was given to the only effective method of hypophosphatasia management —enzyme replacement therapy (ERT). This material is the clinical guideline draft for the management of patients with hypophosphatasia prepared by the Union of Pediatricians of Russia and the Association of Medical Geneticists.

1. Whyte MP. Hypophosphatasia — aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2016;12(4):233–246. doi: 10.1038/nrendo.2016.14.

2. Millán JL, Whyte MP. Alkaline phosphatase and hypophosphatasia. Calcif Tissue Int. 2016;98(4):398–416. doi: 10.1007/s00223-015-0079-1.

3. Mornet E, Yvard A, Taillandier A, et al. A molecular-based estimation of the prevalence of hypophosphatasia in the European population. Ann Hum Genet. 2011;75(3):439–445. doi: 10.1111/j.1469-1809.2011.00642.x.

4. 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.

5. Whyte MP, Zhang F, Wenkert D, et al. Hypophosphatasia: validation and expansion of the clinical nosology for children from 25 years experience with 173 pediatric patients. Bone. 2015;75:229–239. doi: 10.1016/j.bone.2015.02.022.

6. Bishop N, Munns CF, Ozono K. Transformative therapy in hypophosphatasia. Arch Dis Child. 2016;101(6):514–515. doi: 10.1136/archdischild-2015-309579.

7. Anderson HC, Harmey D, Camacho NP, et al. Sustained osteomalacia of long bones despite major improvement in other hypophosphatasia-related mineral deficits in tissue nonspecific alkaline phosphatase/nucleotide pyrophosphatase phosphodiesterase 1 double-deficient mice. Am J Pathol. 2005;166(6):1711–1720. doi: 10.1016/S0002-9440(10)62481-9.

8. Braunstein NА. Multiple fractures, pain, and severe disability in a patient with adult-onset hypophosphatasia. Bone Rep. 2016;4:1–4. doi: 10.1016/j.bonr.2015.10.005.

9. Whyte M. Hypophosphatasia. In: Thakker RV, Whyte MP, Eisman J, Igarashi T, eds. Genetics of bone biology and skeletal disease. London: Academic Press; 2013. pp. 337–360.

10. Whyte MP, Greenberg CR, Salman NJ, et al. Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012;366(10):904–913. doi: 10.1056/NEJMoa1106173.

11. Kishnani PS, Rush ET, Arundel P, et al. Monitoring guidance for patients with hypophosphatasia treated with asfotase alfa. Mol genet metab. 2017;122(1–2):4–17. doi: 10.1016/j.ymgme.2017.07.010.

12. Whyte MP, Coburn SP, Ryan LM, et al. Hypophosphatasia: Biochemical hallmarks validate the expanded pediatric clinical nosology. Bone. 2018;110:96–106. doi: 10.1016/j.bone.2018.01.022.

13. Rush ET. Childhood hypophosphatasia: to treat or not to treat. Orphanet J Rare Dis. 2018;13(1):116. doi: 10.1186/s13023-018-0866-7.

14. Simon S, Resch H, Klaushofer K, et al. Hypophosphatasia: From Diagnosis to Treatment. Curr Rheumatol Rep. 2018;20(11):69. doi: 10.1007/s11926-018-0778-5.

15. Khan AA, Josse R, Kannu P, et al. Hypophosphatasia: Canadian update on diagnosis and management. Osteoporos Int. 2019;30(9):1713–1722. doi: 10.1007/s00198-019-04921-y.

16. Mornet E. Hypophosphatasia. Metabolism. 2018;82:142–155. doi: 10.1016/j.metabol.2017.08.013.

17. Briot K, Roux C. Adult hypophosphatasia. Arch Pediatr. 2017;24(5S2):5S71–5S73. doi: 10.1007/s00198-015-3346-0.