Mucopolysaccharidosis I – clinical manifestations in 24 children from the Czech Republic and Slovakia
Authors:
P. Ješina 1,2; M. Magner 1; H. Poupětová 2; J. Honzíková 2; L. Dvořáková 2; V. Malinová 1; E. Hrubá 2; A. Hlavatá 3; T. Honzík 1,2; K. Veselá 1; P. Sedláček 4; J. Starý 4; J. Zeman 1,2
Authors‘ workplace:
Klinika dětského a dorostového lékařství UK 1. LF a VFN, Praha, přednosta prof. MUDr. J. Zeman, DrSc.
1; Ústav dědičných a metabolických chorob UK 1. LF a VFN, Praha, přednosta doc. MUDr. V. Kožich, CSc.
2; II. detska klinika DFNsP, Bratislava, Slovensko, přednosta prof. MUDr. L. Kovács, DrSc.
3; Klinika dětské hematologie a onkologie UK 2. LF a FN Motol, Praha, přednosta prof. MUDr. J. Starý, DrSc.
4
Published in:
Čes-slov Pediat 2011; 66 (4): 215-225.
Category:
Original Papers
Overview
Mucopolysaccharidosis I (MPS I) is severe metabolic storage disease caused by impaired function of α-L-iduronidase. The aim of this study is to describe clinical symptoms, natural course and to evaluate results of treatment in Czech and Slovak children with MPS I.
Methods:
Study group consists of 24 children from 23 families. In all children diagnosis of MPS I was confirmed on enzymatic level and in 22 children on molecular level.
Results:
First symptoms of disease – hepatosplenomegaly, craniofacial dysmorphy, corneal clouding and psychomotor delay – were observed in all patients. The most of them have macrocephaly (11/21) and skeletal changes – dysostosis multiplex (21/23). Cardiomyopathy with valves impairment (16/21), hearing impairment (9/18), joint stiffness (19/22) and carpal tunnel syndrome (7/23) belongs to later symptoms. All children had increased glycosaminoglycans excretion in urine and decreased activity of α-L-iduronidase in isolated leucocytes. Two mutations in gene α-L-iduronidase were prevalent, the mutation p.W402X was found in 9 and the mutation p.Q70X in 7 children. Hematopoietic stem cell transplantation (HSCT) was performed in 7 children, in 5 of them with good clinical result. 6 children with milder form of disease were treated by a long-lasting enzyme replacement therapy (ERT) with good therapeutic effect, but one patient died due to complication after neurosurgery intervention for compression of cervical spinal cord. The most of children without therapy died (7/11).
Conclusion:
Diagnostic of MPS I in early phases of disease improves prognosis, because correct therapy (HSCT or ERT) can be chosen. Prognosis for children with later diagnosis is very unfavourable. The advance diagnosis is very important also for prenatal diagnostic in affected families.
Key words:
mucopolysaccharidosis I, glycosaminoglycans, α-L-iduronidase, lysosomal storage disorders, enzyme replacement therapy, hematopoietic stem cell transplantation
Sources
1. Hopwood JJ, Morris CP. The mucopolysaccharidosis. Diagnosis, molecular genetics and treatment. Review. Mol Biol Med 1990 Oct; 7(5): 381–404.
2. Martins AM, Dualibi AP, Norato D, et al. Guidelines for the management of mucopolysaccharidosis type I. Review. J Pediatr 2009 Oct; 155(4 Suppl): S32–S46.
3. Poupetová H, Ledvinová J, Berná L, et al. The birth prevalence of lysosomal storage disorders in the Czech Republic: comparison with data in different populations. J Inherit Metab Dis 2010 Aug; 33(4): 387–396. Epub 2010 May 20.
4. Pastores GM, Arn P, Beck M, et al. The MPS I registry: design, methodology, and early findings of a global disease registry for monitoring patients with Mucopolysaccharidosis Type I. Mol Genet Metab 2007 May; 91(1): 37–47. Epub 2007 Mar 2.
5. Wynn RF, Mercer J, Page J, et al. Use of enzyme replacement therapy (Laronidase) before hematopoietic stem cell transplantation for mucopolysaccharidosis I: experience in 18 patients. J Pediatr 2009 Jan; 154(1): 135–139.
6. Beck M. Therapy for lysosomal storage disorders. Review. IUBMB Life 2010 Jan; 62(1): 33–40.
7. Dembure P, Roesel R. Screening for mucopolysaccharidoses by analysis of urinary glycosaminoglycans. In: Hommes FA (ed). Techniques in Diagnostic Human Biochemical Genetics: A Laboratory Manual. New York: Wiley-Liss, Inc., 1991: 77–86.
8. Young EP. Prenatal diagnosis of Hurler disease by analysis of alphaiduronidase in chorionic villi. J Inherit Metab Dis 1992; 15: 224–230.
9. Vazna A, Beesley C, Berna L, et al. Mucopolysaccharidosis type I in 21 Czech and Slovak patients: mutation analysis suggests a functional importance of C-terminus of the IDUA protein. Am J Med Genet A 2009 May; 149A(5): 965–974.
10. Baehner F, Schmiedeskamp C, Krummenauer F, et al. Cumulative incidence rates of the mucopolysaccharidoses in Germany. J Inherit Metab Dis 2005; 28(6): 1011–1017.
11. Poorthuis BJ, Wevers RA, Kleijer WJ, et al. The frequency of lysosomal storage diseases in The Netherlands. Hum Genet 1999; 105: 151–156.
12. Lowry RB, Applegarth DA, Toone JR, et al. An update on the frequency of mucopolysaccharide syndromes in British Columbia. Hum Genet 1990 Aug; 85(3): 389–390.
13. Pastores GM, Arn P, Beck M, Clarke JT, Guffon N, Kaplan P, Muenzer J, Norato DY, Shapiro E, Thomas J, Viskochil D, Wraith JE. The MPS I registry: design, methodology, and early findings of a global disease registry for monitoring patients with Mucopolysaccharidosis Type I. Mol Genet Metab 2007 May; 91(1): 37–47. Epub 2007 Mar 2.
14. Moore D, Connock MJ, Wraith E, et al. The prevalence and survival in Mucopolysaccharidosis I: Hurler, Hurler-Scheie and Scheie syndromes in the UK. Orphanet J Rare Dis 2008 Sep16; 3: 24.
15. Keith O, Scully C, Weidmann GM. Orofacial features of Scheie (Hurler-Scheie) syndrome (alpha-L-iduronidase deficiency). Oral Surg Oral Med Oral Pathol 1990; 70(1): 70–74.
16. Chen SJ, Li YW, Wang TR, Hsu JC. Bony changes in common mucopolysaccharidoses. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 1996 May–Jun; 37(3): 178–184.
17. Kachur E, Del Maestro R. Mucopolysaccharidoses and spinal cord compression: case report and review of the literature with implications of bone marrow transplantation. Review. Neurosurgery 2000 Jul; 47(1): 223–228; discussion: 228–229.
18. Hamilton E, Pitt P. Articular manifestations of Scheie’s syndrome. Ann Rheum Dis 1992 Apr; 51(4): 542–543.
19. Arn P, Wraith JE, Underhill L. Characterization of surgical procedures in patients with mucopolysaccharidosis type I: findings from the MPS I Registry. J Pediatr 2009 Jun; 154(6): 859–864. Epub 2009 Feb 12.
20. Soliman OI, Timmermans RG, Nemes A, et al. Cardiac abnormalities in adults with the attenuated form of mucopolysaccharidosis type I. J Inherit Metab Dis 2007 Oct; 30(5): 750–757. Epub 2007 Jun 14.
21. Dusing SC. Developmental outcomes in children with Hurler syndrome after stem cell transplantation. Dev Med Child Neurol 2007 Sep; 49(9): 646.
22. Cáceres-Marzal C, García-Reymundo M, Solana J, et al. Decreased corneal opacity and improved vision in a patient with mucopolysaccharidosis I (Hurler-Scheie) treated with enzyme replacement therapy (laronidase, Aldurazyme). Am J Med Genet A 2008 Jul 1; 146A(13): 1768–1770.
23. Ashworth JL, Biswas S, Wraith E, et al. The ocular features of the mucopolysaccharidoses. Eye (Lond) 2006 May; 20(5): 553–563.
24. Gocer C, Linthicum FH Jr. Hurler disease. Otol Neurotol 2004 Jan; 25(1): 81–82.
25. Oghan F, Harputluoglu U, Guclu E, et al. Permanent t-tube insertion in two patients with Hurler’s syndrome. Int J Audiol 2007 Feb; 46(2): 94–96.
26. Tomatsu S, Montaño AM, Oguma T, et al. Dermatan sulfate and heparan sulfate as a biomarker for mucopolysaccharidosis I. J Inherit Metab Dis 2010 Apr; 33(2): 141–150. Epub 2010 Feb 17.
27. Fujibayashi S, Minami R, Ishikawa Y, et al. Properties of alpha-L-iduronidase in cultured skin fibroblasts from alpha-L-iduronidase- deficient patients. Hum Genet 1984; 65(3): 268–272.
28. Scott HS, Bunge S, Gal A, et al. Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications. Review. Hum Mutat 1995; 6(4): 288–302.
29. Beesley CE, Meaney CA, Greenland G, et al. Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations. Hum Genet 2001 Nov; 109(5): 503–511. Epub 2001 Oct 19.
30. Terlato NJ, Cox GF. Can mucopolysaccharidosis type I disease severity be predicted based on a patient’s genotype? A comprehensive review of the literature. Genet Med 2003 Jul–Aug; 5(4): 286–294.
31. Scott HS, Nelson PV, Litjens T, et al. Multiple polymorphisms within the alpha-L-iduronidase gene (IDUA): implications for a role in modification of MPS-I disease phenotype. Hum Mol Genet 1993 Sep; 2(9): 1471–1473.
32. Yogalingam G, Guo XH, Muller VJ, et al. Identification and molecular characterization of alpha-L-iduronidase mutations present in mucopolysaccharidosis type I patients undergoing enzyme replacement therapy. Hum Mutat 2004 Sep; 24(3): 199–207.
33. Muenzer J, Wraith JE, Clarke LA. Mucopolysaccharidosis I: management and treatment guidelines. International Consensus Panel on Management and Treatment of Mucopolysaccharidosis I. Pediatrics 2009 Jan; 123(1): 19–29.
34. Aldenhoven M, Boelens JJ, de Koning TJ. The clinical outcome of Hurler syndrome after stem cell transplantation. Review. Biol Blood Marrow Transplant 2008 May; 14(5): 485–498.
35. Valayannopoulos V, de Blic J, Mahlaoui N, et al. Laronidase for cardiopulmonary disease in Hurler syndrome 12 years after bone marrow transplantation. Pediatrics 2010 Nov; 126(5): e1242–e1247. Epub 2010 Oct 25.
36. Giugliani R, Rojas VM, Martins AM, et al. A dose-optimization trial of laronidase (Aldurazyme) in patients with mucopolysaccharidosis I. Mol Genet Metab 2009 Jan; 96(1): 13–19. Epub 2008 Nov 26.
37. Tolar J, Grewal SS, Bjoraker KJ, et al. Combination of enzyme replacement and hematopoietic stem cell transplantation as therapy for Hurler syndrome. Bone Marrow Transplant 2008 Mar; 41(6): 531–535. Epub 2007 Nov 26.
38. Munoz-Rojas MV, Vieira T, Costa R, et al. Intrathecal enzyme replacement therapy in a patient with mucopolysaccharidosis type I and symptomatic spinal cord compression. Am J Med Genet A 2008 Oct 1; 146A(19): 2538–2544.
Labels
Neonatology Paediatrics General practitioner for children and adolescentsArticle was published in
Czech-Slovak Pediatrics
![Issue 4](https://www.prolekare.cz/media/cache/resolve/journal_issue/media/image_pdf/77c93e5c95c4261eeb8942cc69b612ce.jpeg)
2011 Issue 4
Most read in this issue
- Mucopolysaccharidosis I – clinical manifestations in 24 children from the Czech Republic and Slovakia
- Paediatric enteral nutrition: practical approach based on ESPGHAN recommendations
- Arterial cerebral event in childhood
- Breastfeeding rates at the time of hospital discharge in Baby-Friendly and non-Baby-Friendly hospitals in the Czech Republic in 2000–2006