AB082. Phenotype and genotype of Vietnamese patients with mucopolysaccharidosis II: first case series report
Part 4: Oral/poster

AB082. Phenotype and genotype of Vietnamese patients with mucopolysaccharidosis II: first case series report

Le Thi Thuy Hang1, Vu Chi Dung2, Shunji Tomatsu3, Nguyen Thi Yen4, Trinh Thanh Hung5, Can Thi Bich Ngoc2, Ngoc Khanh Nguyen2, Wuh-Liang Hwu6, Gu-Hwan Ki6,7, Han-Wook Yoo7

1Military Medical University, Vietnam; 2National Hospital of Pediatrics, Vietnam; 3Skeletal Dysplasia Lab, Departments of Biomedical Research and Orthopedics ARB 331 Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA; 4Hanoi Medical University, Vietnam; 5Ministry of Science and Technology, Vietnam; 6Department of Pediatrics and Medical Genetics, National Taiwan University Hospital, Taipei, Taiwan; 7Department of Medical Genetics Center, Asan Medical Center, Seoul, Korea

Background and objective: Mucopolysaccharidosis II (MPS II, Hunter syndrome, OMIM 309900) is an X-linked lysosomal storage disorder. MPS II is caused by a deficiency in the enzyme iduronate-2 sulfatase (I2S), leading to the accumulation of the glycosaminoglycans (GAGs) dermatan sulfate and heparan sulfate in lysosomes. Excessive storage of these GAGs causes a variety of clinical manifestations: coarse facies, hearing loss, cardiac valve disease, restrictive and obstructive airway disease, hepatosplenomegaly, skeletal abnormalities, joint contractures, short stature. The study aims to describe clinical characteristics and to identify mutations in the IDS gene in Vietnamese patients with MPS II.

Methods: This case series report including 18 cases with MPS II diagnosed and treated at the National Hospital of Pediatric, Vietnam from December 2012 to May 2015. We describe clinical manifestations, radiological, biochemical evaluations and identified mutations of IDS gene of the patients confirmed by enzyme assay. Nine exons and their intronic boundaries of the IDS gene were sequenced using genomic DNA from the patient. Subsequently, to identify the recombination event with pseudogene, PCR analysis was carried out.

Results: Mean age of diagnosis was 8.2±5.9 years. The clinical symptoms included coarsened facial features (100%); mental retardation and joint stiffness (88.89%); bone deformation (66.67%); hepatomegaly (33.33%); valvular heart disease (22.22%); hearing loss (16.67%); obstructive airway disease (100%). Mutations of IDS gene were identified in 14/18 of cases (77.8%) including six cases (33.33%) had recombination event. Three reported causative mutations were identified: c.120-122del (p.L41del); c.1001A > G (p.D334G); c.879G > C (p.Q293H); and five novel one were identified in this study: c.166dup (p.D56Gfs*2); c.1124-1128dup (p.L377Gfs*10); c.473del (p.Y158fs); c.814C > T (p.Q272*) and c.1048A > T (p.N350Y).

Conclusions: Description of clinical characteristics to predict severity of phenotype and identification of mutations in the IDS gene help in making diagnosis and suitable treatment decision.

Keywords: Mucopolysaccharidosis II (MPS II); IDS gene

Cite this abstract as: Hang LT, Dung VC, Tomatsu S, Yen NT, Hung TT, Ngoc CT, Nguyen NK, Hwu WL, Ki GH, Yoo HW. Phenotype and genotype of Vietnamese patients with mucopolysaccharidosis II: first case series report. Ann Transl Med 2015;3(S2):AB082. doi: 10.3978/j.issn.2305-5839.2015.AB082

Article Options

Download Citation

Share