Enzyme Replacement Therapy and Hematopoietic Stem Cell Transplantation Results in Patients with Hurler Syndrome: Clinical Cases

Mucopolysaccharidosis type I (MPS I) is the hereditary disease characterized with alpha-L-iduronidase activity decrease and further accumulation of heparan and dermatan sulfate in lysosomes. MPS I is rare autosomal recessive disorder with incidence of 0.5–4 cases on 100.000 live-birth infants. Meantime there two approaches in MPS I treatment: hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). HSCT can be the best option for treatment of patients with severe MPS I (Hurler syndrome). Successful engraftment moderates such clinical signs as obstructive airway diseases, hepatosplenomegaly, cardiovascular system dysfunctions. HSCT prevents cognitive functions decline and other pathologic features of central nervous system. Presented clinical cases show various clinical courses according to age of diagnosis, ERT onset and HSCT implementation.

1. Rodgers NJ, Kaizer AM, Miller WP, et al. Mortality after hematopoietic stem cell transplantation for severe mucopolysaccharidosis type I: the 30-year University of Minnesota experience. J Inherit Metab Dis. 2017;40(2):271–280. doi: 10.1007/s10545-016-0006-2.

2. Neufeld EF, Muenzer J. The mucopolysaccharidoses. In: Scriver CR, Beaudet AL, Sly WS, Valle D. The metabolic and molecular basis of inherited disease. 8th edition. New York: McGraw-Hill; 2001. рр. 3421–3452.

3. Moore D, Connock MJ, Wraith E, Lavery C. The prevalence of and survival in mucopolysaccharidosis I: Hurler, Hurler-Scheie and Scheie syndromes in the UK. Orphanet J Rare Dis. 2008;3:24. doi: 10.1186/1750-1172-3-24.

4. Semyachkina AN, Novikov PV, Voskoboyeva EYu, et al. Type I mucopolysaccharidosis: enzyme replacement therapy is a new treatment technology. Rossiiskii vestnik perinatologii i pediatrii. 2012;57(4-1):94–102. (In Russ).

5. Staba SL, Escolar ML, Poe M, et al. Cord-blood transplants from unrelated donors in patients with Hurler’s syndrome. N Engl J Med. 2004;350(19):1960–1969. doi: 10.1056/NEJMoa032613.

6. Meng XL, Shen JS, Ohashi T, et al. Brain transplantation of genetically engineered human neural stem cells globally corrects brain lesions in the mucopolysaccharidosis type VII mouse. J Neurosci Res. 2003;74(2):266–277. doi: 10.1002/jnr.10764.

7. Krivit W, Sung JH, Shapiro EG, Lockman LA. Microglia: the effector cell for reconstitution of the central nervous system following bone marrow transplantation for lysosomal and peroxisomal storage diseases. Cell Transplant. 1995;4(4):385–392. doi: 10.1016/0963-6897(95)00021-o.

8. Buchinskaya NV, Kalashni kova OV, Dubko MF, et al. Mucopolysaccharidosis type I: genetic variants and enzyme replacement therapy experience in Saint-Petersburg. Pediatric. 2013;4(3):41–46. (In Russ).

9. de Ru MH, Boelens JJ, Das AM, et al. Enzyme replacement therapy and/or hematopoietic stem cell transplantation at diagnosis in patients with mucopolysaccharidosis type I: results of a European consensus procedure. Orphanet J Rare Dis. 2011;6:55. doi: 10.1186/1750-1172-6-55.

10. Krivit W. Allogeneic stem cell transplantation for the treatment of lysosomal and peroxisomal metabolic diseases. Springer Semin Immunopathol. 2004;26(1-2):119–132. doi: 10.1007/s00281-004-0166-2.

11. Prasad VK, Kurtzberg J. Emerging trends in transplantation of inherited metabolic diseases. Bone Marrow Transplant. 2008; 41(2):99–108. doi: 10.1038/sj.bmt.1705970.

12. Rovelli AM, Steward CG. Hematopoietic cell transplantation activity in Europe for inherited metabolic diseases: open issues and future directions. Bone Marrow Transplant. 2005;35 Suppl 1: S23–26. doi: 10.1038/sj.bmt.1704839.

13. Tanaka A, Okuyama T, Suzuki Y, et al. Long-term efficacy of hematopoietic stem cell transplantation on brain involvement in patients with mucopolysaccharidosis type II: a nationwide survey in Japan. Mol Genet Metab. 2012;107(3):513–520. doi: 10.1016/j.ymgme.2012.09.004.

14. Valayannopoulos V, Wijburg FA. Therapy for the mucopolysaccharidoses. Rheumatology (Oxford). 2011;50 Suppl 5:v49–59. doi: 10.1093/rheumatology/ker396.

15. Aldenhoven M, Wynn RF, Orchard PJ, et al. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood. 2015;125(13): 2164–2172. doi: 10.1182/blood-2014-11-608075.

16. Noh H, Lee JI. Current and potential therapeutic strategies for mucopolysaccharidoses. J Clin Pharm Ther. 2014;39(3):215–224. doi: 10.1111/jcpt.12136.

17. Tomatsu S, Almeciga-Diaz CJ, Montano AM, et al. Therapies for the bone in mucopolysaccharidoses. Mol Genet Metab. 2015; 114(2):94–109. doi: 10.1016/j.ymgme.2014.12.001.

18. Araya K, Sakai N, Mohri I, et al. Localized donor cells in brain of a Hunter disease patient after cord blood stem cell transplantation. Mol Genet Metab. 2009;98(3):255–263. doi: 10.1016/j.ymgme.2009.05.006.

19. Boelens JJ, Rocha V, Aldenhoven M, et al. Risk factor analysis of outcomes after unrelated cord blood transplantation in patients with Hurler syndrome. Biol Blood Marrow Transplant. 2009;15(5): 618–625. doi: 10.1016/j.bbmt.2009.01.020.

20. Boelens JJ, van Hasselt PM. Neurodevelopmental outcome after hematopoietic cell transplantation in inborn errors of metabolism: current considerations and future perspectives. Neuropediatrics. 2016;47(5):285–292. doi: 10.1055/s-0036-1584602.

21. Boelens JJ, Wynn RF, O’Meara A, et al. Outcomes of hematopoietic stem cell transplantation for Hurler’s syndrome in Europe: a risk factor analysis for graft failure. Bone Marrow Transplant. 2007;40(3):225–233. doi: 10.1038/sj.bmt.1705718.

22. Peters C, Shapiro EG, Anderson J, et al. Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The Storage Disease Collaborative Study Group. Blood. 1998;91(7):2601–2608.

23. Aldenhoven M, Jones SA, Bonney D, et al. Hematopoietic cell transplantation for mucopolysaccharidosis patients is safe and effective: results after implementation of international guidelines. Biol Blood Marrow Transplant. 2015;21(6):1106–1109. doi: 10.1016/j.bbmt.2015.02.011.

24. Tomatsu S, Sawamoto K, Almeciga-Diaz CJ, et al. Impact of enzyme replacement therapy and hematopoietic stem cell transplantation in patients with Morquio A syndrome. Drug Des Devel Ther. 2015;9:1937–1953. doi: 10.2147/DDDT.S68562.

25. Tanjuakio J, Suzuki Y, Patel P, et al. Activities of daily living in patients with Hunter syndrome: impact of enzyme replacement therapy and hematopoietic stem cell transplantation. Mol Genet Metab. 2015;114(2):161–169. doi: 10.1016/j.ymgme. 2014.11.002.

26. Braunlin EA, Stauffer NR, Peters CH, et al. Usefulness of bone marrow transplantation in the Hurler syndrome. Am J Cardiol. 2003;92(7):882–886. doi: 10.1016/s0002-9149(03)00909-3.

27. Herskhovitz E, Young E, Rainer J, et al. Bone marrow transplantation for Maroteaux-Lamy syndrome (MPS VI): long-term follow-up. J Inherit Metab Dis. 1999;22(1):50–62. doi: 10.1023/ A:1005447232027.

28. Muenzer J. Overview of the mucopolysaccharidoses. Rheuma tology (Oxford). 2011;50 Suppl 5:v4–12. doi: 10.1093/ rheumatology/ker394.

29. Boelens JJ, Aldenhoven M, Purtill D, et al. Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning. Blood. 2013; 121(19):3981–3987. doi: 10.1182/blood-2012-09-455238.

30. Rovelli AM. The controversial and changing role of haematopoietic cell transplantation for lysosomal storage disorders: an update. Bone Marrow Transplant. 2008;41 Suppl 2:S87–89. doi: 10.1038/bmt.2008.62.

31. Weisstein JS, Delgado E, Steinbach LS, et al. Musculoskeletal manifestations of Hurler syndrome: long-term follow-up after bone marrow transplantation. J Pediatr Orthop. 2004;24(1):97–101. doi: 10.1097/01241398-200401000-00019.

32. Dickson P, Peinovich M, McEntee M, et al. Immune tolerance improves the efficacy of enzyme replacement therapy in canine mucopolysaccharidosis I. J Clin Invest. 2008;118(8):2868–2876. doi: 10.1172/JCI34676.

33. Kakkis ED, Muenzer J, Tiller GE, et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med. 2001;344(3): 182–188. doi: 10.1056/NEJM200101183440304.

34. Ghosh A, Miller W, Orchard PJ, et al. Enzyme replacement therapy prior to haematopoietic stem cell transplantation in mucopolysaccharidosis type I: 10-year combined experience of 2 centres. Mol Genet Metab. 2016;117(3):373–377. doi: 10.1016/j.ymgme. 2016.01.011.

35. Wraith JE, Beck M, Lane R, et al. Enzyme replacement therapy in patients who have mucopolysaccharidosis I and are younger than 5 years: results of a multinational study of recombinant human alpha-L-iduronidase (laronidase). Pediatrics. 2007;120(1):e37–46. doi: 10.1542/peds.2006–2156.

36. Biffi A. Hematopoietic stem cell gene therapy for storage disease: current and new indications. Mol Ther. 2017;25(5): 1155–1162. doi: 10.1016/j.ymthe.2017.03.025.

37. Kubaski F, Yabe H, Suzuki Y, et al. Hematopoietic stem cell transplantation for patients with mucopolysaccharidosis II. Biol Blood Marrow Transplant. 2017;23(10):1795–1803. doi: 10.1016/j.bbmt.2017.06.020.

38. Wynn RF, Wraith JE, Mercer J, et al. Improved metabolic correction in patients with lysosomal storage disease treated with hematopoietic stem cell transplant compared with enzyme replacement therapy. J Pediatr. 2009;154(4):609–611. doi: 10.1016/j.jpeds.2008.11.005.

39. Wang J, Luan Z, Jiang H, et al. Allogeneic hematopoietic stem cell transplantation in thirty-four pediatric cases of mucopolysaccharidosis-A ten-year report from the China Children Transplant Group. Biol Blood Marrow Transplant. 2016;22(11): 2104–2108. doi: 10.1016/j.bbmt.2016.08.015.

40. Mitchell R, Nivison-Smith I, Anazodo A, et al. Outcomes of haematopoietic stem cell transplantation for inherited metabolic disorders: a report from the Australian and New Zealand Children’s Haematology Oncology Group and the Australasian Bone Marrow Transplant Recipient Registry. Pediatr Transplant. 2013;17(6): 582–588. doi: 10.1111/petr.12109.

41. Vellodi A, Young EP, Cooper A, et al. Bone marrow transplantation for mucopolysaccharidosis type I: experience of two British centres. Arch Dis Child. 1997;76(2):92–99. doi: 10.1136/adc.76.2.92.

42. Orchard PJ, Milla C, Braunlin E, et al. Pre-transplant risk factors affecting outcome in Hurler syndrome. Bone Marrow Transplant. 2010;45(7):1239–1246. doi: 10.1038/bmt.2009.319.

43. Cox-Brinkman J, Boelens JJ, Wraith JE, et al. Haematopoietic cell transplantation (HCT) in combination with enzyme replacement therapy (ERT) in patients with Hurler syndrome. Bone Marrow Transplant. 2006;38(1):17–21. doi: 10.1038/sj.bmt.1705401.

44. Australian Government Department of Health. Life Saving Drugs Program: Information for patients, prescribers and pharmacists [Internet]. Guidelines for the treatment of mucopolysaccharidosis type I (MPS I) [updated 2019 May 10]. Available from: https://www1. health.gov.au/internet/main/publishing.nsf/Content/lsdp-criteria.

45. Prasad VK, Kurtzberg J. Cord blood and bone marrow transplantation in inherited metabolic diseases: scientific basis, current status and future directions. Br J Haematol. 2010;148(3):356–372. doi: 10.1111/j.1365-2141.2009.07974.x.

46. Prasad VK, Mendizabal A, Parikh SH, et al. Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes. Blood. 2008;112(7):2979–2989. doi: 10.1182/blood-2008-03-140830.

47. Baxter MA, Wynn RF, Schyma L, et al. Marrow stromal cells from patients affected by MPS I differentially support haematopoietic progenitor cell development. J Inherit Metab Dis. 2005;28(6): 1045–1053. doi: 10.1007/s10545-005-0136-4.

48. Ferrara G, Maximova N, Zennaro F, et al. Hematopoietic stem cell transplantation effects on spinal cord compression in Hurler. Pediatr Transplant. 2014;18(3):E96–99. doi: 10.1111/petr.12231.

49. Pievani A, Azario I, Antolini L, et al. Neonatal bone marrow transplantation prevents bone pathology in a mouse model of mucopolysaccharidosis type I. Blood. 2015;125(10):1662–1671. doi: 10.1182/blood-2014-06-581207.

50. Kurtzberg J. Early HSCT corrects the skeleton in MPS. Blood. 2015;125(10):1518–1519. doi: 10.1182/blood-2014-11-606681.

51. Barth AL, de Magalhaes TS, Reis AB, et al. Early hema topoietic stem cell transplantation in a patient with severe mucopolysaccharidosis II: A 7 years follow-up. Mol Genet Metab Rep. 2017;12:62–68. doi: 10.1016/j.ymgmr.2017.05.010.