title: Mucopolysaccharidosis type II in females and response to enzyme replacement therapy.
abstract: Mucopolysaccharidosis type II (MPS II, Hunter syndrome) is an X-linked lysosomal storage disease caused by a deficiency of iduronate-2-sulfatase (IDS). Two affected girls with moderate and severe forms of MPS II with normal karyotypes and increased urinary dermatan sulphate and heparin sulphate excretion and marked deficiencies of IDS activity are reported. Molecular studies showed that case 1 has a heterozygous mutation c.1568A > G (p.Y523C) associated with almost totally skewed inactivation of the normal maternal X chromosome, and case 2 has a heterozygous deletion that includes exons 1-4 of IDS (minimal deletion range c.1-103_184del). The multi-exon deletion correlated with early onset of the disease and severe phenotype with intellectual disability, whereas the missense mutation was associated with moderate developmental delay. Although genotype-phenotype correlation in MPS II is difficult, gene deletions seem to correlate with more severe clinical manifestation of the disease. Enzyme replacement therapy (ERT) in these two females resulted in disease stabilization in both.
authors.affiliation: Department of Metabolic Diseases, The Children's Memorial Health Institute, Warsaw, Polandd. ajurecka@gmail.com
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Jurecka
authors.forename: Zita
authors.initials: Z
authors.lastname: Krumina
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Żuber
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Różdżyńska-Świątkowska
authors.forename: Anna
authors.initials: A
authors.lastname: Kłoska
authors.forename: Barbara
authors.initials: B
authors.lastname: Czartoryska
authors.forename: Anna
authors.initials: A
authors.lastname: Tylki-Szymańska
mesh_terms: D002648:Child; D002675:Child, Preschool; D003871:Dermatan Sulfate / Q000652:urine; D056947:Enzyme Replacement Therapy; D005260:Female; D006493:Heparin / Q000652:urine; D006579:Heterozygote; D006801:Humans; D007066:Iduronate Sulfatase / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use*; D016532:Mucopolysaccharidosis II / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D009154:Mutation
chemical_list: D003871:Dermatan Sulfate; D006493:Heparin; D007066:Iduronate Sulfatase