• MeSH
• dospělí MeSH
• lidé MeSH
• mukopolysacharidóza II * MeSH
• stenóza průdušnice * MeSH
• stenty MeSH
• trachea chirurgie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• Brain MRI, Hunter disease, Peripheral nerve sonography,
• MeSH
• dospělí MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mozek patologie   MeSH
• mukopolysacharidóza II diagnostické zobrazování   patologie   MeSH
• neurozobrazování MeSH
• periferní nervový systém diagnostické zobrazování   patologie   MeSH
• ultrasonografie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

• MeSH
• dítě MeSH
• elektronová mikroskopie MeSH
• lidé MeSH
• mukopolysacharidóza I genetika   patologie   MeSH
• mukopolysacharidóza II genetika   patologie   MeSH
• mukopolysacharidózy genetika   patologie   MeSH
• předškolní dítě MeSH
• retinopathia pigmentosa genetika   patologie   MeSH
• syndrom MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH

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.

• Klíčová slova
• Hunter syndrome, MPS II, Slavic origin, genotype-phenotype correlation, mucopolysaccharidosis type II,
• MeSH
• dítě MeSH
• dospělí MeSH
• genetické asociační studie MeSH
• glykoproteiny genetika   MeSH
• glykosaminoglykany moč   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mukopolysacharidóza II etiologie   genetika   MeSH
• mutace * MeSH
• předškolní dítě MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Chorvatsko MeSH
• Slovenská republika MeSH
• Srbsko MeSH
• Názvy látek
• glykoproteiny MeSH
• glykosaminoglykany MeSH
• IDS protein, human MeSH Prohlížeč

• MeSH
• hluchota diagnóza   MeSH
• kojenec MeSH
• lidé MeSH
• mukopolysacharidóza I klasifikace   diagnóza   MeSH
• mukopolysacharidóza II klasifikace   diagnóza   MeSH
• předškolní dítě MeSH
• retinopathia pigmentosa klasifikace   diagnóza   MeSH
• syndrom MeSH
• tělesná výška MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• eponyma * MeSH
• lidé MeSH
• nemoc * MeSH
• syndrom * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• dítě MeSH
• hlas * MeSH
• kvalita hlasu * MeSH
• lidé MeSH
• mukopolysacharidóza II * patofyziologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

BACKGROUND: Mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by defects in genes coding for different lysosomal enzymes which degrade glycosaminoglycans. Impaired lysosomal degradation causes cell dysfunction leading to progressive multiorgan involvement, disabling consequences and poor life expectancy. Enzyme replacement therapy (ERT) is now available for most MPS types, offering beneficial effects on disease progression and improving quality of life of patients. The landscape of MPS in Europe is not completely described and studies on availability of treatment show that ERT is not adequately implemented, particularly in Southern and Eastern Europe. In this study we performed a survey analysis in main specialist centers in Southern and Eastern European countries, to outline the picture of disease management in the region and understand ERT implementation. Since the considerable number of MPS IVA patients in the region, particularly adults, the study mainly focused on MPS IVA management and treatment. RESULTS: 19 experts from 14 Southern and Eastern European countries in total responded to the survey. Results outlined a picture of MPS management in the region, with a high number of MPS patients managed in the centers and a high level of care. MPS II was the most prevalent followed by MPS IVA, with a particular high number of adult patients. The study particularly focused on management and treatment of MPS IVA patients. Adherence to current European Guidelines for follow-up of MPS IVA patients is generally adequate, although some important assessments are reported as difficult due to the lack of MPS skilled specialists. Availability of ERT in Southern and Eastern European countries is generally in line with other European regions, even though regulatory, organizational and reimbursement constrains are demanding. CONCLUSIONS: The landscape of MPS in Southern and Eastern European countries is generally comparable to that of other European regions, regarding epidemiology, treatment accessibility and follow up difficulties. However, issues limiting ERT availability and reimbursement should be simplified, to start treatment as early as possible and make it available for more patients. Besides, educational programs dedicated to specialists should be implemented, particularly for pediatricians, clinical geneticists, surgeons, anesthesiologists and neurologists.

• Klíčová slova
• Enzyme replacement therapy, Morquio A syndrome, Mucopolysaccharidoses, Southern and Eastern European countries, Treatment accessibility,
• MeSH
• dospělí MeSH
• enzymová substituční terapie metody   MeSH
• kvalita života MeSH
• lidé MeSH
• mukopolysacharidóza II * farmakoterapie   MeSH
• mukopolysacharidóza IV * farmakoterapie   MeSH
• mukopolysacharidózy * farmakoterapie   terapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Mucopolysaccharidosis type II (MPS II) is an X-linked lysosomal storage disorder resulting from deficiency of iduronate-2-sulphatase activity. The disease manifests almost exclusively in males; only 16 symptomatic heterozygote girls have been reported so far. We describe the results of X-chromosome inactivation analysis in a 5-year-old girl with clinically severe disease and heterozygous mutation p.Arg468Gln in the IDS gene. X inactivation analysed at three X-chromosome loci showed extreme skewing (96/4 to 99/1) in two patient's cell types. This finding correlated with exclusive expression of the mutated allele. Induced pluripotent stem cells (iPSC) generated from the patient's peripheral blood demonstrated characteristic pluripotency markers, deficiency of enzyme activity, and mutation in the IDS gene. These cells were capable of differentiation into other cell types (cardiomyocytes, neurons). In MPS II iPSC clones, the X inactivation ratio remained highly skewed in culture conditions that led to partial X inactivation reset in Fabry disease iPSC clones. Our data, in accordance with the literature, suggest that extremely skewed X inactivation favouring the mutated allele is a crucial condition for manifestation of MPS II in females. This suggests that the X inactivation status and enzyme activity have a prognostic value and should be used to evaluate MPS II in females. For the first time, we show generation of iPSC from a symptomatic MPS II female patient that can serve as a cellular model for further research of the pathogenesis and treatment of this disease.

• MeSH
• iduronátsulfatasa genetika   metabolismus   MeSH
• inaktivace chromozomu X * MeSH
• indukované pluripotentní kmenové buňky * MeSH
• kultivované buňky MeSH
• lidé MeSH
• mukopolysacharidóza II diagnóza   enzymologie   genetika   MeSH
• mutace MeSH
• předškolní dítě MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• iduronátsulfatasa MeSH

INTRODUCTION: Myelodysplastic syndromes (MDS) are classified as oncohematologic, clonal diseases. However, some MDS subtypes lack malignant clinical features. Literary data on the clonality of blood cells in MDS are controversial. Therefore we examined the clonality in the group of our own MDS patients. We were especially interested in the comparison of the clonality of myeloid and lymphoid cell line-ages. METHODS AND MATERIAL: Using X-chromosome inactivation methods based on polymorphism in human androgen receptor gene (HUMARA), iduronate sulphatase gene (IDS) and protein p55 gene, we assessed the clonality of granulocytes, monocytes and T-lymphocytes of 49 female patients with MDS and 12 control women of various ages. RESULTS: Though the results were heterogeneous, certain trends were observed: most frequently monoclonality of monocytes was found (51%), granulocytes were monoclonal in 33% of cases, monoclonal T lymphocytes only in 8% of cases. There was no case with monoclonal T lymphocytes and simultaneously polyclonal myeloid cell fractions. Results differ in relation to the subtypes of MDS. Among controls we observed monoclonality of myeloid cells in one case of an old lady. WE CONCLUDE: The results confirm the presence of malignant clone of myeloid cells in MDS, which can be of variable size. The examination of the clonality in MDS can be significant for the therapy decision. Monoclonal myeloid cells are found least frequently in refractory anemia, most frequently in RAEB-T. Monoclonality of cells in sideroblastic anemia is interesting. The prevailing polyclonality of T lymphocytes in MDS can be explained by the presence of a long-lived cell population originating from the period before the development of MDS. The role of the polyclonal memory T cells in the antitumor immunity in MDS is discussed.

• MeSH
• androgenní receptory genetika   MeSH
• buněčné klony MeSH
• dospělí MeSH
• granulocyty MeSH
• iduronátsulfatasa genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monocyty MeSH
• myelodysplastické syndromy genetika   MeSH
• onkogenní protein p55(v-myc) genetika   MeSH
• polymorfismus genetický MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• T-lymfocyty MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• androgenní receptory MeSH
• iduronátsulfatasa MeSH
• onkogenní protein p55(v-myc) MeSH