Top

Published in:

Open Access 01-12-2017 | Research

Clinical, biochemical and molecular characteristics of Filipino patients with mucopolysaccharidosis type II - Hunter syndrome

Authors: Mary Anne D. Chiong, Daffodil M. Canson, Mary Ann R. Abacan, Melissa Mae P. Baluyot, Cynthia P. Cordero, Catherine Lynn T. Silao

Published in: Orphanet Journal of Rare Diseases | Issue 1/2017

Abstract

Background

Mucopolysaccharidosis type II, an X-linked recessive disorder is the most common lysosomal storage disease detected among Filipinos. This is a case series involving 23 male Filipino patients confirmed to have Hunter syndrome. The clinical and biochemical characteristics were obtained and mutation testing of the IDS gene was done on the probands and their female relatives.

Results

The mean age of the patients was 11.28 (SD 4.10) years with an average symptom onset at 1.2 (SD 1.4) years. The mean age at biochemical diagnosis was 8 (SD 3.2) years. The early clinical characteristics were developmental delay, joint stiffness, coarse facies, recurrent respiratory tract infections, abdominal distention and hernia. Majority of the patients had joint contractures, severe intellectual disability, error of refraction, hearing loss and valvular regurgitation on subspecialists’ evaluation. The mean GAG concentration was 506.5 mg (SD 191.3)/grams creatinine while the mean plasma iduronate-2-sulfatase activity was 0.86 (SD 0.79) nmol/mg plasma/4 h. Fourteen (14) mutations were found: 6 missense (42.9%), 4 nonsense (28.6%), 2 frameshift (14.3%), 1 exon skipping at the cDNA level (7.1%), and 1 gross insertion (7.1%). Six (6) novel mutations were observed (43%): p.C422F, p.P86Rfs*44, p.Q121*, p.L209Wfs*4, p.T409R, and c.1461_1462insN[710].

Conclusion

The age at diagnosis in this series was much delayed and majority of the patients presented with severe neurologic impairment. The results of the biochemical tests did not contribute to the phenotypic classification of patients. The effects of the mutations were consistent with the severe phenotype seen in the majority of the patients.

Martin R, Beck M, Eng C, Guigliani R, Harmatz P, Munoz V, et al. Recognition and diagnosis of Mucopolysaccharidosis II (Hunter syndrome). Pediatrics. 2008;121:e377–85.CrossRefPubMed

Neufeld E, Muenzer J. The Mucopolysaccharidoses. In: Scriver C, Sly W, Childs B, Beaudet A, Valle D, Kinzler K, Vogelstein B, editors. The Metabolic and Molecular Bases of Inherited Disease. New York: McGraw-Hill; 2001. p. 3421–52.

Vafiadaki E, Cooper A, Heptinstall L, Hatton C, Thornley M, Wraith J. Mutation analysis in 57 unrelated patients with MPS II (Hunter disease). Arch Dis Child. 1998;79:237–41.CrossRefPubMedPubMedCentral

Lin S, Chang J, Lee-Chen G, Lin D, Lin H, Chuang C. Detection of Hunter syndrome (mucopolysaccharidosis type II) in Taiwanese: biochemical and linkage studies of the iduronate-2-sulfatase gene defects in MPS II patients and carriers. Clin Chim Acta. 2006;369:29–34.CrossRefPubMed

Froissart R, Moreira Da Silva I, Maire I. Mucopolysaccharidosis type II: an update on mutation spectrum. Acta Paediatr. 2007;96:71–7.CrossRefPubMed

Galvis J, Gonzalez J, Uribe A, Velasco H. Deep genotyping of the IDS gene in Colombian patients with Hunter syndrome. J Inherit Metab Dis. 2015;19:101–9.

Li P, Bellows A, Thompson J. Molecular basis of iduronate-2-sulphatase gene mutations in patients with mucopolysaccharidosis type II (Hunter syndrome). J Med Genet. 1999;36:21–7.PubMedPubMedCentral

Cudry S, Tigaud I, Froissart R, Bonnet V, Maire I, Bozon D. MPS II in females: molecular basis of two different cases. J Med Genet. 2002;37:e29.CrossRef

Ricci V, Regis S, Duca M, Filocamo M. An Alu-mediated rearrangement as cause of exon skipping in Hunter disease. Hum Genet. 2003;112:419–25.PubMed

10.

Schwartz I, Ribeiro M, Mota J, Toralles M, Correia P, Horovitz D, et al. A clinical study of 77 patients with Mucopolysaccharidosis type II. Acta Paediatr. 2007;96:63–70.CrossRefPubMed

11.

Burton BK, Guigliani R. Diagnosing Hunter syndrome in pediatric practice: practical considerations and common pitfalls. Eur J Pediatr. 2012;171:631–9.CrossRefPubMedPubMedCentral

12.

Wraith J, Beck M, Giugliani R, Clarke J, Martin R, Muenzer J, On Behalf Of The HOS Investigators. Initial report from the Hunter Outcome Survey. Genet Med. 2008;10:508–16.CrossRefPubMed

13.

Young I, Harper P, Newcombe R, Archer I. A clinical and genetic study of Hunter’s syndrome. 2 differences between mild and severe forms. J Med Genet. 1982;19:408–11.CrossRefPubMedPubMedCentral

14.

Arn P, Bruce IA, Wraith J, Travers H, Fallet S. Airway related symptoms and surgeries in patients with Mucopolysaccharidosis type I. Ann Otol Rhinol Laryngol. 2015;124:198–205.CrossRefPubMedPubMedCentral

15.

Kampmann C, Beck M, Morin I, Loehr J. Prevalence and characterization of cardiac involvement in Hunter syndrome. J Pediatr. 2011;159:327–31.CrossRefPubMed

16.

Lee O, Kim S, Sohn Y, Park H, Lee S, Kim C. A study of the relationship between clinical phenotypes and plasma iduronate-2-sulfatase enzyme activities in hunter syndrome patients. Korean J Pediatr. 2012;55:88–92.CrossRefPubMedPubMedCentral

17.

Tomatsu S, Gutierrez MA, Ishimaru T, Peña OM, Montaño AM, Maeda H, et al. Heparan sulfate levels in mucopolysaccharidoses and mucolipidoses. J Inherit Metab Dis. 2005;28:743–57.CrossRefPubMed

18.

Froissart R, Maire I, Millat G, Cudry S, Birot AM, Bonnet V, et al. Identification of iduronate sulfatase gene alterations in 70 unrelated Hunter patients. Clin Genet. 1998;53:362–8.CrossRefPubMed

19.

Isogai K, Sukegawa K, Tomatsu S, Fukao T, Song XQ, Yamada Y, et al. Mutation analysis in the iduronate-2-sulphatase gene in 43 Japanese patients with Mucopolysaccharidosis type II (Hunter disease). J Inherit Metab Dis. 1998;21:60–70.CrossRefPubMed

20.

Brusius-Facchin A, Schwartz I, Zimmer C, Ribeiro M, Acosta A, Horovitz D. Mucopolysaccharidosis type II: identification of 30 novel mutations among Latin American patients. Mol Genet Metab. 2014;111:133–8.CrossRefPubMed

21.

Popowska E, Rathmann M, Tylki-Szymanska A, Bunges, Steglich C, Schwinger E, et al. Mutations of the iduronate-2-sulfatase gene in 12 Polish patients with mucopolysaccharidosis type II. Hum Mutat. 1995;5:97–100.CrossRefPubMed

22.

Rathmann M, Bunge S, Beck M, Kresse H, Tylki-Szymanska A, Gal A. Mucopolysaccharidosis type II (Hunter syndrome): mutation hot spots in the iduronate-2-sulfatase gene. Am J Hum Genet. 1996;59:1202–9.PubMedPubMedCentral

23.

Crotty P, Braun S, Anderson R, Whitley C. Mutation R468W of the iduronate-2-sulfatase gene in mild Hunter syndrome (mucopolysaccharidosis type II) confirmed by in vitro mutagenesis and expression. Hum Mol Genet. 1992;1:755–7.CrossRefPubMed

24.

Whitley C, Anderson R, Aronovich E, Crotty P, Anyane-Yeboa K, Russo D, et al. Caveat to genotype-phenotype correlation in mucopolysaccharidosis type II: discordant clinical severity of R468W and R468Q mutations of the iduronate-2-sulfatase gene. Hum Mutat. 1993;2:235–7.CrossRefPubMed

25.

Kato T, Kato Z, Kuratsubo I, Tanaka N, Ishigami T, Kajihara J, et al. Mutational and structural analysis of Japanese patients with mucopolysaccharidosis type II. J Hum Genet. 2005;50:395–402.CrossRefPubMed

26.

Zhang H, Li J, Zhang X, Wang Y, Qiu W, Ye J, Han L, Gao X, Gu X. Analysis of the IDS gene in 38 patients with Hunter syndrome: the c.879G > A (p.Gln293Gln) synonymous variation in a female create exonic splicing. PLoS One. 2011;6:e22951.CrossRefPubMedPubMedCentral

27.

Flomen R, Green P, Bentley D, Giannelli F, Green E. Detection of point mutations and gross deletion in six Hunter syndrome patients. Genomics. 1992;13:543–50.CrossRefPubMed

28.

Keeratichamroen S, Ketudat Cairns J, Wattanasirichaigoon D, Wasant P, Ngiwsara L, Suwannarat P, et al. Molecular analysis of iduronate-2-sulfatase gene in Thai patients with Hunter syndrome. J Inherit Metab Dis. 2008;31 Suppl 2:S303–11.CrossRefPubMed

29.

Kosuga M, Mashima R, Hirakiyama A, Fuji N, Kumagai T, Seo JH, Nikaido M, Saito S, Ohno K, Sakuraba H, Okuyama T. Molecular diagnosis of 65 families with mucopolysaccharidosis type II (Hunter syndrome) characterized by 16 novel mutations in the IDS gene: Genetic, pathological, and structural studies on iduronate-2-sulfatase. Mol Genet Metab. 2016;118:190–7.CrossRefPubMed

Title: Clinical, biochemical and molecular characteristics of Filipino patients with mucopolysaccharidosis type II - Hunter syndrome
Authors: Mary Anne D. Chiong
Daffodil M. Canson
Mary Ann R. Abacan
Melissa Mae P. Baluyot
Cynthia P. Cordero
Catherine Lynn T. Silao
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Orphanet Journal of Rare Diseases / Issue 1/2017
Electronic ISSN: 1750-1172
DOI: https://doi.org/10.1186/s13023-016-0558-0

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Clinical, biochemical and molecular characteristics of Filipino patients with mucopolysaccharidosis type II - Hunter syndrome

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2017

STUB1/CHIP mutations cause Gordon Holmes syndrome as part of a widespread multisystemic neurodegeneration: evidence from four novel mutations

Identification of GAA variants through whole exome sequencing targeted to a cohort of 606 patients with unexplained limb-girdle muscle weakness

Phenotype prediction for mucopolysaccharidosis type I by in silico analysis

A survey of resistance to colchicine treatment for French patients with familial Mediterranean fever

The burden of amyloid light chain amyloidosis on health-related quality of life

Autosomal recessive inherited bleeding disorders in Pakistan: a cross-sectional study from selected regions