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Mucopolysaccharidosis III in Mainland China: natural history, clinical and molecular characteristics of 34 patients

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Veröffentlicht/Copyright: 24. Mai 2020
Journal of Pediatric Endocrinology and Metabolism
Aus der Zeitschrift Journal of Pediatric Endocrinology and Metabolism Band 33 Heft 6

Abstract

Objectives

Sanfilippo syndrome (Mucopolysaccharidosis III, MPS III) is a rare autosomal recessive hereditary disease, which is caused by lysosomal enzyme deficiency. This study was operated to investigate clinical and molecular characteristics of patients with MPS III, which will improve the diagnosis and treatment of MPS III.

Method

Thirty four patients with MPS III were assessed using clinical evaluation, questionnaire, and scoring system.

Results

Among the 34 patients, 14 had MPS IIIA, 19 had MPS III B, and one had MPS III C. Speech delay (100%) and intellectual disability (100%) were the most prevalent clinical manifestations in this cohort, followed by hyperactivity (94.12%), hirsutism (91.18%), enlarged head circumference (73.52%), repeated diarrhea (67.64%), sparse teeth (67.64%), and Mongolian spots (64.71%). There were two clinical manifestations that were significantly different between IIIA and IIIB: Hepatosplenomegaly and serrated teeth. The most common initial symptoms at diagnosis were speech delay (52.94%), hyperactivity (35.29%), and mental retardation (29.41%). Genetic analysis of 25 patients was conducted, which identified 12 novel mutations.

Conclusion

When language retardation, mental retardation, and rough facial features occurred, MPS III should be considered. At same time, more examination should be operated, such as examination of changes in cranial magnetic resonance imaging of cerebral cortex atrophy. Hepatosplenomegaly and serrated teeth could be used clinically to preliminarily distinguish IIIA from IIIB.

Keywords: lysosomal storage disease; mucopolysaccharidosis III (MPS III); mucopolysaccharide storage syndrome type III; sanfilippo syndrome
Corresponding author: Yan Meng, Department of Pediatrics, Chinese PLA General Hospital, Beijing, 100853, China, E-mail:

Weijing Kong and Yan Meng contributed equally to this work.

Funding source: The National Key Research and Development Program of China

Award Identifier / Grant number: 2016YFC1000707

Acknowledgments

We acknowledge the participation of study patients and their families. The authors thank Dr. Cheng Lu for his assistance in biostatistics. The authors are grateful to Dr. Shunji Tomatsu for helping to make the questionnaire.

  1. Funding: This case report was supported by The National Key Research and Development Program of China (2016YFC1000707).

  2. Author contributions: YG, WJ and SXY managed and followed up the case. KWJ collected the data and wrote the manuscript. ZLP supervised the management and follow up of the case. MY supervised the management and follow up of the case, and the writing of the article. All authors read and approved the final manuscript.

  3. Competing interests: The authors declare that they have no competing interests.

  4. Ethics approval and consent to participate: We obtained informed consent from all participating patients (or their parents or carers) in accordance with the tenets of the Declaration of Helsinki. This study received approval from the Institutional Review Board of the Chinese PLA General Hospital in Beijing, China.

  5. Consent for publication: Not applicable.

  6. Availability of data and material: Data from patients can be made available from the corresponding author after discussion with the Institutional Review Board. Consent from participants for data sharing was not obtained but any shared data will be anonymised.

References

1. Valstar MJ, Ruijter GJ, van Diggelen OP, Poorthuis BJ, Wijburg FA. Sanfilippo syndrome: a mini-review. J Inherit Metab Dis 2008;31:240–52. https://doi.org/10.1007/s10545-008-0838-5.Suche in Google Scholar

2. Chinen Y, Tohma T, Izumikawa Y, Uehara H, Ohta T. Sanfilippo type B syndrome: five patients with an R565P homozygous mutation in the alpha-N-acetylglucosaminidase gene from the Okinawa islands in Japan. J Hum Genet 2005;50:357–9. https://doi.org/10.1007/s10038-005-0258-4.Suche in Google Scholar

3. Klein U, Kresse H, von Figura K. Sanfilippo syndrome type C: deficiency of acetyl-CoA:alpha-glucosaminide N-acetyltransferase in skin fibroblasts. Proc Natl Acad Sci USA 1978;75:5185–9. https://doi.org/10.1073/pnas.75.10.5185.Suche in Google Scholar

4. Kresse H, Paschke E, von Figura K, Gilberg W, Fuchs W. Sanfilippo disease type D: deficiency of N-acetylglucosamine-6-sulfate sulfatase required for heparan sulfate degradation. Proc Natl Acad Sci U S A 1980;77:6822–6. https://doi.org/10.1073/pnas.77.11.6822.Suche in Google Scholar

5. Kleijer WJ, Janse HC, Vosters RP, Niermeijer MF, van de Kamp JJ. First-trimester diagnosis of mucopolysaccharidosis IIIA (Sanfilippo A disease). N Engl J Med 1986;314:185-6. https://doi.org/10.1056/nejm198601163140319.Suche in Google Scholar

6. Fedele AO. Sanfilippo syndrome: causes, consequences, and treatments. Appl Clin Genet 2015;8:269–81. https://doi.org/10.2147/tacg.s57672.Suche in Google Scholar

7. Bilginer Gurbuz B, Aypar E, Coskun T, Alehan D, Dursun A, Tokatli A, et al. The effectiveness of enzyme replacement therapy on cardiac findings in patients with mucopolysaccharidosis. J Pediatr Endocrinol Metab 2019;32:1049–53. https://doi.org/10.1515/jpem-2019-0293.Suche in Google Scholar

8. Zelei T, Csetneki K, Voko Z, Siffel C. Epidemiology of Sanfilippo syndrome: results of a systematic literature review. Orphanet J Rare Dis 2018;13:53. https://doi.org/10.1186/s13023-018-0796-4.Suche in Google Scholar

9. Heron B, Mikaeloff Y, Froissart R, Caridade G, Maire I, Caillaud C, et al. Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece. Am J Med Genet A 2011;155A:58–68. https://doi.org/10.1002/ajmg.a.33779.Suche in Google Scholar

10. Baehner F, Schmiedeskamp C, Krummenauer F, Miebach E, Bajbouj M, Whybra C, et al. Cumulative incidence rates of the mucopolysaccharidoses in Germany. J Inherit Metab Dis 2005;28:1011–7. https://doi.org/10.1007/s10545-005-0112-z.Suche in Google Scholar

11. Lin HY, Chuang CK, Lee CL, Tu RY, Lo YT, Chiu PC, et al. Mucopolysaccharidosis III in Taiwan: Natural history, clinical and molecular characteristics of 28 patients diagnosed during a 21-year period. Am J Med Genet A 2018;176:1799–809. https://doi.org/10.1002/ajmg.a.40351.Suche in Google Scholar

12. Karpova EA, Voznyi Ya V, Keulemans JL, Hoogeveen AT, Winchester B, Tsvetkova IV, et al. A fluorimetric enzyme assay for the diagnosis of Sanfilippo disease type A (MPS IIIA). J Inherit Metab Dis 1996;19:278–85. https://doi.org/10.1007/bf01799255.Suche in Google Scholar

13. Marsh J, Fensom AH. 4-Methylumbelliferyl alpha-N-acetylglucosaminidase activity for diagnosis of Sanfilippo B disease. Clin Genet 1985;27:258–62. https://doi.org/10.1111/j.1399-0004.1985.tb00217.x.Suche in Google Scholar

14. Voznyi Ya V, Karpova EA, Dudukina TV, Tsvetkova IV, Boer AM, Janse HC, et al. A fluorimetric enzyme assay for the diagnosis of Sanfilippo disease C (MPS III C). J Inherit Metab Dis 1993;16:465–72. https://doi.org/10.1007/bf00710299.Suche in Google Scholar

15. He W, Voznyi Ya V, Boer AM, Kleijer WJ, van Diggelen OP. A fluorimetric enzyme assay for the diagnosis of Sanfilippo disease type D (MPS IIID). J Inherit Metab Dis 1993;16:935–41. https://doi.org/10.1007/bf00711508.Suche in Google Scholar

16. Beesley CE, Jackson M, Young EP, Vellodi A, Winchester BG. Molecular defects in Sanfilippo syndrome type B (mucopolysaccharidosis IIIB). J Inherit Metab Dis 2005;28:759–67. https://doi.org/10.1016/j.ymgme.2012.11.042.Suche in Google Scholar

17. Beesley CE, Young EP, Vellodi A, Winchester BG. Identification of 12 novel mutations in the alpha-N-acetylglucosaminidase gene in 14 patients with Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB). J Med Genet 1998;35:910–4. https://doi.org/10.1136/jmg.35.11.910.Suche in Google Scholar

18. Beesley CE, Young EP, Vellodi A, Winchester BG. Mutational analysis of Sanfilippo syndrome type A (MPS IIIA): identification of 13 novel mutations. J Med Genet 2000;37:704–7. https://doi.org/10.1136/jmg.37.9.704.Suche in Google Scholar

19. Brady J, Trehan A, Landis D, Toro C. Mucopolysaccharidosis type IIIB (MPS IIIB) masquerading as a behavioural disorder. BMJ Case Rep 2013;2013. https://doi.org/10.1136/bcr-2013-009592.Suche in Google Scholar

20. Di Natale P, Pontarelli G, Villani GR, Di Domenico C. Gene symbol: SGSH. disease: Sanfilippo type A syndrome, mucopolysaccharidosis IIIA. Hum Genet 2006;119:679.Suche in Google Scholar

21. Hettiarachchi D, Nethikumara N, Pathirana B, Weththasigha K, Dissanayake WDN, Dissanayake VHW. A novel mutation in the NAGLU gene associated with Sanfilippo syndrome type B (mucopolysaccharidosis III B). Clin Case Rep 2018;6:1051–4. https://doi.org/10.1002/ccr3.1521.Suche in Google Scholar

22. Muschol N, Storch S, Ballhausen D, Beesley C, Westermann JC, Gal A, et al. Transport, enzymatic activity, and stability of mutant sulfamidase (SGSH) identified in patients with mucopolysaccharidosis type III A. Hum Mutat 2004;23:559–66. https://doi.org/10.1002/humu.20037.Suche in Google Scholar

23. Tang J, Pan J, Guo Y, Ai Y, Jiang W, Du M, et al. Mucopolysaccharidosis type IIIB mutations in Chinese patients: identification of two novel NAGLU mutations and analysis of two cases involving prenatal diagnosis. Clin Chim Acta 2013;419:33–8. https://doi.org/10.1016/j.cca.2013.01.009.Suche in Google Scholar

24. Weber B, Guo XH, Kleijer WJ, van de Kamp JJ, Poorthuis BJ, Hopwood JJ. Sanfilippo type B syndrome (mucopolysaccharidosis III B): allelic heterogeneity corresponds to the wide spectrum of clinical phenotypes. Eur J Hum Genet 1999;7:34–44. https://doi.org/10.1038/sj.ejhg.5200242.Suche in Google Scholar

25. Weber B, Guo XH, Wraith JE, Cooper A, Kleijer WJ, Bunge S, et al. Novel mutations in Sanfilippo A syndrome: implications for enzyme function. Hum Mol Genet 1997;6:1573–9. https://doi.org/10.1093/hmg/6.9.1573.Suche in Google Scholar

26. Wen Z, Cheng TL, Yin DZ, Sun SB, Wang Z, Yu SY, et al. Identification of the genetic cause for childhood disintegrative disorder by whole-exome sequencing. Neurosci Bull. 2017;33:251–4. https://doi.org/10.1007/s12264-017-0119-0.Suche in Google Scholar

27. Zhao HG, Aronovich EL, Whitley CB. Genotype-phenotype correspondence in Sanfilippo syndrome type B. Am J Hum Genet 1998;62:53–63. https://doi.org/10.1086/301682.Suche in Google Scholar

28. Zeng Q, Fan Y, Wang L, Huang Z, Gu X, Yu Y. Molecular defects identified by whole exome sequencing in a child with atypical mucopolysaccharidosis IIIB. J Pediatr Endocrinol Metab 2017;30:463–9. https://doi.org/10.1515/jpem-2016-0333.Suche in Google Scholar

29. Delgadillo V, O'Callaghan Mdel M, Gort L, Coll MJ, Pineda M. Natural history of Sanfilippo syndrome in Spain. Orphanet J Rare Dis 2013;8:189. https://doi.org/10.1186/1750-1172-8-189.Suche in Google Scholar

30. Malm G, Mansson JE. Mucopolysaccharidosis type III (Sanfilippo disease) in Sweden: clinical presentation of 22 children diagnosed during a 30-year period. Acta Paediatr 2010;99:1253–7. https://doi.org/10.1111/j.1651-2227.2010.01800.x.Suche in Google Scholar

31. Meyer A, Kossow K, Gal A, Muhlhausen C, Ullrich K, Braulke T, et al. Scoring evaluation of the natural course of mucopolysaccharidosis type IIIA (Sanfilippo syndrome type A). Pediatrics 2007;120:e1255–61. https://doi.org/10.1542/peds.2007-0282.Suche in Google Scholar

32. Ruijter GJ, Valstar MJ, van de Kamp JM, van der Helm RM, Durand S, van Diggelen OP, et al. Clinical and genetic spectrum of Sanfilippo type C (MPS IIIC) disease in The Netherlands. Mol Genet Metab 2008;93:104–11. https://doi.org/10.1016/j.ymgme.2007.09.011.Suche in Google Scholar

33. Shapiro EG, Nestrasil I, Delaney KA, Rudser K, Kovac V, Nair N, et al. A prospective natural history study of mucopolysaccharidosis type IIIA. J Pediatr 2016;170:278–87 e1-4. https://doi.org/10.1016/j.jpeds.2015.11.079.Suche in Google Scholar

34. Truxal KV, Fu H, McCarty DM, McNally KA, Kunkler KL, Zumberge NA, et al. A prospective one-year natural history study of mucopolysaccharidosis types IIIA and IIIB: implications for clinical trial design. Mol Genet Metab 2016;119:239–48. https://doi.org/10.1016/j.ymgme.2016.08.002.Suche in Google Scholar

35. Whitley CB, Cleary M, Eugen Mengel K, Harmatz P, Shapiro E, Nestrasil I, et al. Observational prospective natural history of patients with sanfilippo syndrome type B. J Pediatr 2018;197:198–206 e2. https://doi.org/10.1016/j.jpeds.2018.01.044.Suche in Google Scholar

36. Faverio P, Stainer A, De Giacomi F, Gasperini S, Motta S, Canonico F, et al. Molecular pathways and respiratory involvement in lysosomal storage diseases. Int J Mol Sci 2019;20. https://doi.org/10.3390/ijms20030751.Suche in Google Scholar

37. Souza-Fernandes AB, Pelosi P, Rocco PR. Bench-to-bedside review: the role of glycosaminoglycans in respiratory disease. Crit Care 2006;10:237. https://doi.org/10.1186/cc5069.Suche in Google Scholar

38. White KK, Karol LA, White DR, Hale S. Musculoskeletal manifestations of Sanfilippo syndrome (mucopolysaccharidosis type III). J Pediatr Orthop 2011;31:594–8. https://doi.org/10.1097/bpo.0b013e31821f5ee9.Suche in Google Scholar

39. Nicolas-Jilwan M, AlSayed M. Mucopolysaccharidoses: overview of neuroimaging manifestations. Pediatr Radiol 2018;48:1503–20. https://doi.org/10.1007/s00247-018-4139-3.Suche in Google Scholar

40. Lin HY, Lin SP, Chuang CK, Niu DM, Chen MR, Tsai FJ, et al. Incidence of the mucopolysaccharidoses in Taiwan, 1984–2004. Am J Med Genet A 2009;149A:960–4. https://doi.org/10.1002/ajmg.a.32781.Suche in Google Scholar

41. Velasco HM, Sanchez Y, Martin AM, Umana LA. Natural history of sanfilippo syndrome type c in Boyaca, Colombia. J Child Neurol 2017;32:177–83. https://doi.org/10.1177/0883073816672391.Suche in Google Scholar

42. Buhrman D, Thakkar K, Poe M, Escolar ML. Natural history of Sanfilippo syndrome type A. J Inherit Metab Dis 2014;37:431–7. https://doi.org/10.1007/s10545-013-9661-8.Suche in Google Scholar

Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/jpem-2019-0505).

Received: 2019-10-27
Accepted: 2020-03-23
Published Online: 2020-05-24

© 2020 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Original Articles
  3. Genetic characteristics and follow-up of patients with fatty acid β-oxidation disorders through expanded newborn screening in a Northern Chinese population
  4. Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism
  5. Institutional experience of newborn screening for inborn metabolism disorders by tandem MS in the Turkish population
  6. Investigation of the effect of epicardial adipose tissue thickness on cardiac conduction system in children with type 1 diabetes mellitus
  7. Retrospective evaluation of 85 patients with urea cycle disorders: one center experience, three new mutations
  8. Circulating chemerin level may be associated with early vascular pathology in obese children without overt arterial hypertension – preliminary results
  9. A novel diagnostic tool for the evaluation of hypothalamic-pituitary region and diagnosis of growth hormone deficiency: pons ratio
  10. Growth status of children and adolescents born small for gestational age at full term in Korea: data from the KNHANES-V
  11. Children with onset-ketoacidosis are admitted to the nearest hospital available, regardless of center size
  12. Evaluation of α-klotho level in insulin dependent diabetes mellitus (IDDM) children
  13. Evaluation of the relationship between the one-hour plasma glucose concentration and beta-cell functions and cardiometabolic parameters during oral glucose tolerance test in obese children and adolescents
  14. Triglycerides/high-density lipoprotein cholesterol is a predictor similar to the triglyceride–glucose index for the diagnosis of metabolic syndrome using International Diabetes Federation criteria of insulin resistance in obese adolescents: a cross-sectional study
  15. Rapid progressive central precocious puberty: diagnostic and predictive value of basal sex hormone levels and pelvic ultrasound
  16. Mucopolysaccharidosis III in Mainland China: natural history, clinical and molecular characteristics of 34 patients
  17. Case Reports
  18. An infant presenting with extreme hypertriglyceridemia diagnosed as glycogen storage disease type Ia
  19. A novel heterozygous mutation in the insulin receptor gene presenting with type A severe insulin resistance syndrome
  20. Isolated premature menarche in two siblings with Neurofibromatosis type 1
  21. GAD-65 autoantibody associated epilepsy
https://doi.org/10.1515/jpem-2019-0505
Schlagwörter für diesen Artikel
lysosomal storage disease; mucopolysaccharidosis III (MPS III); mucopolysaccharide storage syndrome type III; sanfilippo syndrome

Artikel in diesem Heft

  1. Frontmatter
  2. Original Articles
  3. Genetic characteristics and follow-up of patients with fatty acid β-oxidation disorders through expanded newborn screening in a Northern Chinese population
  4. Clinical and genetic investigation of 136 Japanese patients with congenital hypothyroidism
  5. Institutional experience of newborn screening for inborn metabolism disorders by tandem MS in the Turkish population
  6. Investigation of the effect of epicardial adipose tissue thickness on cardiac conduction system in children with type 1 diabetes mellitus
  7. Retrospective evaluation of 85 patients with urea cycle disorders: one center experience, three new mutations
  8. Circulating chemerin level may be associated with early vascular pathology in obese children without overt arterial hypertension – preliminary results
  9. A novel diagnostic tool for the evaluation of hypothalamic-pituitary region and diagnosis of growth hormone deficiency: pons ratio
  10. Growth status of children and adolescents born small for gestational age at full term in Korea: data from the KNHANES-V
  11. Children with onset-ketoacidosis are admitted to the nearest hospital available, regardless of center size
  12. Evaluation of α-klotho level in insulin dependent diabetes mellitus (IDDM) children
  13. Evaluation of the relationship between the one-hour plasma glucose concentration and beta-cell functions and cardiometabolic parameters during oral glucose tolerance test in obese children and adolescents
  14. Triglycerides/high-density lipoprotein cholesterol is a predictor similar to the triglyceride–glucose index for the diagnosis of metabolic syndrome using International Diabetes Federation criteria of insulin resistance in obese adolescents: a cross-sectional study
  15. Rapid progressive central precocious puberty: diagnostic and predictive value of basal sex hormone levels and pelvic ultrasound
  16. Mucopolysaccharidosis III in Mainland China: natural history, clinical and molecular characteristics of 34 patients
  17. Case Reports
  18. An infant presenting with extreme hypertriglyceridemia diagnosed as glycogen storage disease type Ia
  19. A novel heterozygous mutation in the insulin receptor gene presenting with type A severe insulin resistance syndrome
  20. Isolated premature menarche in two siblings with Neurofibromatosis type 1
  21. GAD-65 autoantibody associated epilepsy
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