Research Report

JIMD Reports, Volume 33

Volume 33 of the series JIMD Reports pp 19-25

Date:

Clinical and Genetic Characteristics of Romanian Patients with Mucopolysaccharidosis Type II

  • Camelia AlkhzouzAffiliated with1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy Email author 
  • , Cecilia LazeaAffiliated with1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy
  • , Simona BucerzanAffiliated with1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy
  • , Ioana NascuAffiliated with1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy
  • , Eva KissAffiliated with1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy
  • , Carmencita Lucia DenesAffiliated with1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy
  • , Paula Grigorescu-SidoAffiliated with1st Department of Pediatrics, Iuliu Haţieganu University of Medicine and Pharmacy

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Abstract

Background: Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is a rare X-linked disorder caused by deficiency of iduronate-2-sulfatase (I2S) enzyme, which leads to the accumulation of partially digested glycosaminoglycans (GAGs) in the lysosomes and induces multisystemic alteration (coarse facial features; skeletal dysplasia; hepatosplenomegaly; joint stiffness and contractures; heart, lung, vision, and hearing disability; profound neurological decline).

The purpose of this study is to present the clinical and genetic characteristics of Romanian patients with Hunter syndrome and the genotype–phenotype correlation.

Material and Methods: 15 unrelated patients, with MPS II ranging from mild (4 subjects) to severe phenotype (11 subjects) aged 2 to 20 years, were evaluated clinically, cognitive development, enzyme assay and molecular analysis.

Results: The molecular analysis of the 15 unrelated Romanian MPS II patients has identified 15 different mutations (2 major genetic defects (13%) and 13 minor genetic defects (87%)): microdeletions and point mutations (missense, nonsense), seven of them described for the first time—deletion encompassing 3 to exon 7; c823G>T, pD275Y; c.1600A>C (pN534H); c.102_10delAG (p.D5Cfs*11); c.448_471del (p.P150_P157del); c.421delA (p.I141Yfs*72); and c.419-1G>C. The major genetic defects were correlated with a severe course of disease.

Conclusion: This is the first study on the clinical and molecular characterization of the MPS II Romanian patients. This study supports the evidence of the mutational heterogeneity of the I2S gene as well as the difficulty to correlate genotype and phenotype in the patients with MPS II.

Keywords

Hunter disease Mucopolysaccharidosis type II Romania