title: Genotype-phenotype correlation in 44 Czech, Slovak, Croatian and Serbian patients with mucopolysaccharidosis type II.
abstract: Mucopolysaccharidosis type II (Hunter syndrome, MPS II, OMIM 309900) is an X-linked lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase (IDS). We analyzed clinical and laboratory data from 44 Slavic patients with this disease. In total, 21 Czech, 7 Slovak, 9 Croatian and 7 Serbian patients (43 M/1 F) were included in the study (median age 11.0 years, range 1.2-43 years). Birth prevalence ranged from 1:69,223 (Serbia) to 1:192,626 (Czech Rep.). In the majority of patients (71%), the disease manifested in infancy. Cognitive functions were normal in 10 patients. Four, six and 24 patients had mild, moderate, and severe developmental delay, respectively, typically subsequent to developmental regression (59%). Residual enzyme activity showed no predictive value, and estimation of glycosaminoglycans (GAGs) had only limited importance for prognosis. Mutation analysis performed in 36 families led to the identification of 12 novel mutations, eight of which were small deletions/insertions. Large deletions/rearrangements and all but one small deletion/insertion led to a severe phenotype. This genotype-phenotype correlation was also identified in six cases with recurrent missense mutations. Based on patient genotype, the severity of the disease may be predicted with high probability in approximately half of MPS II patients.
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Dvorakova
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
authors.forename: H
authors.initials: H
authors.lastname: Vlaskova
authors.affiliation: Department of Metabolism and Clinical Genetics, Mother and Child Health Care Institute of Serbia, Belgrade, Serbia.|School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: A
authors.initials: A
authors.lastname: Sarajlija
authors.affiliation: Department of Pediatrics, University Hospital Center, Zagreb, Croatia.
authors.forename: D P
authors.initials: DP
authors.lastname: Ramadza
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
authors.forename: H
authors.initials: H
authors.lastname: Poupetova
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
authors.forename: E
authors.initials: E
authors.lastname: Hruba
authors.affiliation: 2nd Department of Pediatrics, Comenius University Medical School in Bratislava University Children's Hospital, Bratislava, Slovakia.
authors.forename: A
authors.initials: A
authors.lastname: Hlavata
authors.affiliation: 1st Department of Pediatrics, Comenius University Medical School in Bratislava University Children's Hospital, Bratislava, Slovakia.
authors.forename: V
authors.initials: V
authors.lastname: Bzduch
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
authors.forename: K
authors.initials: K
authors.lastname: Peskova
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
authors.forename: G
authors.initials: G
authors.lastname: Storkanova
authors.affiliation: Department of Metabolism and Clinical Genetics, Mother and Child Health Care Institute of Serbia, Belgrade, Serbia.
authors.forename: B
authors.initials: B
authors.lastname: Kecman
authors.affiliation: Department of Metabolism and Clinical Genetics, Mother and Child Health Care Institute of Serbia, Belgrade, Serbia.|School of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: M
authors.initials: M
authors.lastname: Djordjevic
authors.affiliation: Department of Pediatrics, University Hospital Center and University of Zagreb, School of Medicine, Zagreb, Croatia.
authors.forename: I
authors.initials: I
authors.lastname: Baric
authors.affiliation: Department of Laboratory Diagnostics, University Hospital Centre Zagreb and School of Medicine, Zagreb, Croatia.
authors.forename: K
authors.initials: K
authors.lastname: Fumic
authors.affiliation: Department of Paediatrics, Children's Hospital Zagreb, School of Medicine, Zagreb, Croatia.
authors.forename: I
authors.initials: I
authors.lastname: Barisic
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Reboun
authors.affiliation: Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Kulhanek
authors.affiliation: Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.|Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
authors.forename: J
authors.initials: J
authors.lastname: Zeman
authors.affiliation: Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
authors.forename: M
authors.initials: M
authors.lastname: Magner
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D017523:Croatia; D018153:Czech Republic; D005260:Female; D056726:Genetic Association Studies; D006023:Glycoproteins / Q000235:genetics; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D007223:Infant; D008297:Male; D016532:Mucopolysaccharidosis II / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D055771:Serbia; D018154:Slovakia; D055815:Young Adult
chemical_list: D006023:Glycoproteins; D006025:Glycosaminoglycans; C018322:IDS protein, human
keywords: Hunter syndrome; MPS II; Slavic origin; genotype-phenotype correlation; mucopolysaccharidosis type II