Современные подходы к ведению детей с гипофосфатазией

Гипофосфатазия — редкое генетическое заболевание, обусловленное дефицитом тканенеспецифической щелочной фосфатазы в результате мутации в гене ALPL. В зависимости от формы и тяжести болезнь может дебютировать внутриутробно, в детском возрасте или у взрослых. В статье представлены современные сведения об эпидемиологии, этиологии и клинических проявлениях гипофосфатазии у детей, подробно освещаются этапы дифференциально-диагностического поиска, приведены рекомендации по лечению, основанные на принципах доказательной медицины. При отсутствии своевременного лечения прогноз болезни в большинстве случаев неблагоприятный для жизни. Пациенты нуждаются в наблюдении мультидисциплинарной командой врачей. Единственным эффективным методом лечения является ферментозаместительная терапия асфотазой альфа; необходимо также проводить симптоматическую терапию, а при реабилитации пациентов использовать физиотерапевтические процедуры и лечебные физкультурные комплексы упражнений.

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

2. Millan JL, Whyte MP. Alkaline phosphatase and hypophosphatasia. Calcif Tissue Int. 2016;98(4):398-416. doi: https://doi.org/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: https://doi.org/10.1111/j.1469-1809.2011.00642.x

4. Гуркина Е.Ю., Воинова В.Ю., Кузенкова Л.М. и др. Гипофосфатазия. Обзор клинических случаев, опубликованных в РФ // РМЖ. — 2021. — № 2. — С. 42-48.

5. Tsang T, Raghuwanshi MP. Hypophosphatasia Misdiagnosed as Osteoporosis in a Young Girl. J Endocr Soc. 2021;5(Suppl 1):A201-A202. doi: https://doi.org/10.1210/jendso/bvab048.409

6. 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: https://doi.org/10.1016/j.bone.2015.02.022

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

8. 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: https://doi.org/10.1016/S0002-9440(10)62481-9

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

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

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

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

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

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

15. Mornet E. Hypophosphatasia. Metabolism. 2018;82:142-155. doi: https://doi.org/10.1016/j.metabol.2017.08.013

16. Briot K, Roux C. Adult hypophosphatasia. Arch Pediatr. 2017;24(5S2):5S71-5S73. doi: https://doi.org/10.1016/S0929-693X(18)30018-6

17. 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: https://doi.org/10.1016/j.ymgme.2017.07.010

18. Michigami T, Ohata Y, Fujiwara M, et al. Clinical Practice Guidelines for Hypophosphatasia. Clin Pediatr Endocrinol. 2020;29(1):9-24. doi: https://doi.org/10.1297/cpe.29.9

19. Estey MP, Cohen AH, Colantonio DA, et al. CLSI-based transference of the CALIPER database of pediatric reference intervals from Abbott to Beckman, Ortho, Roche and Siemens Clinical Chemistry Assays: direct validation using reference samples from the CALIPER cohort. Clin Biochem. 2013;46(13-14):1197-1219. doi: https://doi.org/10.1016/j.clinbiochem.2013.04.001

20. Ройтман А.П., Мамедов И.С., Сухоруков В.С. Референтные интервалы активности щелочной фосфатазы у детей в сыворотке крови. Лабораторная диагностика гипофосфатазии // Лабораторная служба. — 2015. — Т. 4. — № 1. — С. 35-41. — doi: https://doi.org/10.17116/labs20154135-41

21. Whyte MP, Leung E, Wilcox W, et al. Hypophosphatasia: a retrospective natural history study of the severe perinatal and infantile forms. In: 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.

22. Villa-Suarez JM, Garci'a-Fontana C, Andujar-Vera F, et al. Hypophosphatasia: A Unique Disorder of Bone Mineralization. Int J Mol Sci. 2021;22(9):4303. doi: https://doi.org/10.3390/ijms22094303

23. Christine Hofmann C, Girschick H, Mornet E, et al. Unexpected high intrafamilial phenotypic variability observed in hypophosphatasia. Eur J Hum Genet. 2914;22(10):1160-1164. doi: https://doi.org/10.1038/ejhg.2014.10

24. Mornet E. Molecular Genetics of Hypophosphatasia and Phenotype-Genotype Correlations. Subcell Biochem. 2015;76:25-43. doi: https://doi.org/10.1007/978-94-017-7197-9_2

25. Ishiguro T, Sugiyama Y, Ueda K, et al. Findings of amplitude-integrated electroencephalogram recordings and serum vitamin B6 metabolites in perinatal lethal hypophosphatasia during enzyme replacement therapy. Brain Dev. 2019;41(8):721-725. doi: https://doi.org/10.1016/j.braindev.2019.03.015

26. Martos-Moreno GA, Calzada J, Couce ML, Argente J. Hypophosphatasia: Clinical manifestations, diagnostic recommendations and therapeutic options. An Pediatr (Engl Ed). 2018;88(6):356. e1-356.e11. doi: https://doi.org/10.1016/j.anpedi.2017.06.004

27. Fukazawa M, Tezuka J, Sasazuki M, et al. Infantile hypophosphatasia combined with vitamin B6-responsive seizures and reticular formation lesions on magnetic resonance imaging: A case report. Brain Dev. 2018;40(2):140-144. doi: https://doi.org/10.1016/j.braindev.2017.07.015

28. Di Rocco F, Baujat G, Cormier-Daire V, et al. Craniosynostosis and hypophosphatasia. Arch Pediatr. 2017;24(5S2):5S89-5S92. doi: https://doi.org/10.1016/S0929-693X(18)30022-8

29. Vogt M, Girschick H, Schweitzer T, et al. Pediatric hypophos-phatasia: lessons learned from a retrospective single-center chart review of 50 children. Orphanet J Rare Dis. 2020;15(1):212. doi: https://doi.org/10.1186/s13023-020-01500-x

30. Collmann H, Mornet E, Gattenlohner S, et al. Neurosurgical aspects of childhood hypophosphatasia. Childs Nerv Syst. 2009;25(2):217-223. doi: https://doi.org/10.1007/s00381-008-0708-3

31. Graham BL, Steenbruggen I, Miller MR, et al. Standardization of Spirometry 2019 Update. An Official American Thoracic Society and European Respiratory Society Technical Statement. Am J Respir Crit Care Med. 2019;200(8):e70-e88. doi: https://doi.org/10.1164/rccm.201908-1590ST

32. Beydon N, Davis SD, Lombardi E, et al. An official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children. Am J Respir Crit Care Med. 2007;175(12):1304-1345. doi: https://doi.org/10.1164/rccm.200605-642ST

33. Kamran A, Jennings RW. Tracheomalacia and Tracheobronchomalacia in Pediatrics: An Overview of Evaluation, Medical Management, and Surgical Treatment. Front Pediatr. 2019;7:512. doi: https://doi.org/10.3389/fped.2019.00512

34. Nunes ME. Hypophosphatasia. In: GeneReviews® [Internet]. Adam MP, Everman DB, Mirzaa GM, et al., eds. Seattle (WA): University of Washington, Seattle; 1993-2022.

35. Whyte MP, Rockman-Greenberg C, Ozono K, et al. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. J Clin Endocrinol Metab. 2016;101(1):334-342. doi: https://doi.org/10.1210/jc.2015-3462

36. Vislobokova E, Kiselnikova L, Voinova V, Sholokhova N. Dental findings in patients with hypophosphatasia. Scientific Abstracts of the 14th Congress of the European Academy of Paediatric Dentistry (EAPD) Palazzo dei Congressi, Lake Lugano, Switzerland 20th to 23rd June 2018. Eur Arch Paediatr Dent. 2019;20:152. doi: https://doi.org/10.1007/s40368-018-0390-4

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

38. Kitaoka T, Tajima T, Nagasaki K, et al. Safety and efficacy of treatment with asfotase alfa in patients with hypophosphatasia: Results from a Japanese clinical trial. Clin Endocrinol (Oxf). 2017;87(1):10-19. doi: https://doi.org/10.1111/cen.13343

39. Yamamoto H, Sasamoto Y, Miyamoto Y, et al. A successful treatment with pyridoxal phosphate for West syndrome in hypophosphatasia. Pediatr Neurol. 2004;30(3):216-218. doi: https://doi.org/10.1016/j.pediatrneurol.2003.08.003

40. de Roo MGA, Abeling NGGM, Majoie CB, et al. Infantile hypophosphatasia without bone deformities presenting with severe pyridoxine-resistant seizures. Mol Genet Metab. 2014;111(3):404-407. doi: https://doi.org/10.1016/j.ymgme.2013.09.014

41. Belachew D, Kazmerski T, Libman I, et al. Infantile hypophosphatasia secondary to a novel compound heterozygous mutation presenting with pyridoxine-responsive seizures. JIMD Rep. 2013;11:17-24. doi: https://doi.org/10.1007/8904_2013_217

42. Taketani T. Neurological Symptoms of Hypophosphatasia. Subcell Biochem. 2015;76:309-322. doi: https://doi.org/10.1007/978-94-017-7197-9_14

43. Nunes ML, Mugnol F, Bica I, Fiori RM. Pyridoxine-dependent seizures associated with hypophosphatasia in a newborn. J Child Neurol. 2002;17(3):222-224. doi: https://doi.org/10.1177/088307380201700314

44. Girschick HJ, Schneider P, Haubitz I, et al. Effective NSAID treatment indicates that hyperprostaglandinism is affecting the clinical severity of childhood hypophosphatasia. Orphanet J Rare Dis. 2006;1:24. doi: https://doi.org/10.1186/1750-1172-1-24

45. Bianchi ML, Bishop NJ, Guanabens N, et al. Hypophosphatasia in adolescents and adults: overview of diagnosis and treatment. Osteoporos Int. 2020 31(8):1445-1460. doi: https://doi.org/10.1007/s00198-020-05345-9

46. Correa Marquez RR, Behari G. Hypophosphatasia (HPP) Treatment & Management. In: Medscape. Updated: Jun 05, 2023. Available online: https://emedicine.medscape.com/article/945375-treatment#d6. Accessed on July 15, 2023.

47. Miyashita S, Ochiai S, Sakamoto С, et al. VP13.10: Prenatal ultrasound findings in a survived case of perinatal lethal hypophosphatasia with enzyme replacement therapy started early in life. Ultrasound Obstet Gynecol. 2020;56(S1):104-104. doi: https://doi.org/10.1002/uog.22519

48. Yang Y, Liu Z, Wei L, et al. Prosthodontic Rehabilitation of a Patient with Hypophosphatasia Using Dental Implants: A Case Report with Seven Years Follow-Up. J Prosthodont. 2021;30(9):742-746. doi: https://doi.org/10.1111/jopr.13419

49. Tournis S, Yavropoulou MP, Polyzos SA, Doulgeraki A. Hypophosphatasia. J Clin Med. 2021;10(23):5676. doi: https://doi.org/10.3390/jcm10235676

50. Linglart A, Biosse-Duplan M. Hypophosphatasia. Curr Osteoporos Rep. 2016;14(3):95-105. doi: https://doi.org/10.1007/s11914-016-0309-0

51. Simon S, Resch H. Treatment of hypophosphatasia. Wien Med Wochenschr. 2020;170(5-6):112-115. doi: https://doi.org/10.1007/s10354-020-00736-3

52. Коняхина Г.П., Захарова Н.А. Лечебная физкультура для детей с ограниченными возможностями здоровья: учебно-методическое пособие. — Челябинск; 2019. — 81 с.

53. Медико-психологическая помощь детям с нарушением психического развития в системе комплексной реабилитации: методические рекомендации. — М.: ДЗМ; 2018. — № 83. — 28 с.

54. Leung EC, Mhanni AA, Reed M, et al. Outcome of perinatal hypophosphatasia in manitoba mennonites: a retrospective cohort analysis. JIMD Rep. 2013;11:73-78. doi: https://doi.org/10.1007/8904_2013_224