Mapping the genetic and clinical characteristics of Gaucher disease in the Iberian Peninsula

<p>Abstract</p> <p>Background</p> <p>Gaucher disease (GD) is due to deficiency of the glucocerebrosidase enzyme. It is panethnic, but its presentation reveals ethnicity-specific characteristics.</p> <p>Methods</p> <p>We evaluated the distribution, and clinical and genetic characteristics of GD patients in the Iberian Peninsula (IP). We analysed geographical distribution, demographic, genetic and clinical data, age at diagnosis, type, and years of therapy in 436 GD patients from the IP.</p> <p>Results</p> <p>The prevalence of GD was 1/149,000 inhabitants; 88.3% were type 1, 6.7% type 2, and 5.0% type 3. The mean age at diagnosis in type 1 was 28.7 years. A total of 72.7% were classified as having mild forms, 25.5% moderate, and 1.7% severe. Anemia and thrombocytopenia were present in 56% and 55%, respectively. Bone disease and hepatomegaly were reported in 62% and 68%, respectively, and were more likely in asplenic than in non-splenectomized patients. Sixty-nine mutant alleles were identified, and five mutations accounted for 75% of the <it>GBA </it>alleles. Several patients described in our series had interesting phenotypes. A total of 58.7% of patients had received enzyme replacement therapy and 12.6% were treated with miglustat.</p> <p>Conclusions</p> <p>A broad spectrum of <it>GBA </it>mutations is present in the IP, with 98.2% of type 1 GD being mild and 23.0% never treated. These data highlight genetic and phenotypic heterogeneities among geographic populations.</p

Factors associated with body image dissatisfaction in a Brazilian university sample during the COVID-19 pandemic

We investigated the prevalence of body image dissatisfaction (BID) and associated factors among professors and undergraduate students in Brazil during the COVID-19 pandemic. Using Stunkard’s Figure Rating Scale, BID was analyzed in a sample of 2,220 adults. The independent variables were sociodemographic, lifestyle, mental health symptoms, COVID-19-related factors, disordered eating, experience of weight stigma, and weight change concerns. We used a multinomial logistic regression analysis. The overall prevalence of BID was 82.5% (69.0% due to excess weight), with more professors dissatisfied by excess weight than undergraduate students (78.9% vs. 61.2%, p &lt; 0.001). In the adjusted model, being a young adult (PR, 1.201, 95% CI: 1.128; 1.279), married or in a stable union (PR, 1.088, 95% CI: 1.027; 1.152), reporting of binge eating episode (PR, 1.120, 95% CI: 1.068; 1.173), concern about weight gain (PR, 1.394, 95% CI: 1.310; 1,483), and experience of excess weight stigma (PR, 1.193, 95% CI: 1.141; 1.248) increased the prevalence of BID due to excess weight. While males (PR, 1.578, 95% CI: 1.328; 1.875), moderate to severe depressive symptoms (PR, 1.217, 95% CI: 1.011; 1.465), the concern of losing weight (PR, 1.494, 95% CI: 1.221; 1.830), and experience of low weight stigma (PR, 2.620, 95% CI: 2.093; 3.280) increased the prevalence of BID due to low weight. Different factors associated with BID were observed between students and professors. Bearing in mind the complexity of body image, it is essential to consider different public health interventions and the COVID-19 pandemic’s influence on reducing BID among Brazilian adults, especially susceptible groups

Enzyme replacement therapy for mucopolysaccharidosis VI: evaluation of long-term pulmonary function in patients treated with recombinant human N-acetylgalactosamine 4-sulfatase

Pulmonary function is impaired in untreated mucopolysaccharidosis type VI (MPS VI). Pulmonary function was studied in patients during long-term enzyme replacement therapy (ERT) with recombinant human arylsulfatase B (rhASB; rhN-acetylgalactosamine 4-sulfatase). Pulmonary function tests prior to and for up to 240 weeks of weekly infusions of rhASB at 1 mg/kg were completed in 56 patients during Phase 1/2, Phase 2, Phase 3 and Phase 3 Extension trials of rhASB and the Survey Study. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and, in a subset of patients, maximum voluntary ventilation (MVV), were analyzed as absolute volume in liters. FEV1 and FVC showed little change from baseline during the first 24 weeks of ERT, but after 96 weeks, these parameters increased over baseline by 11% and 17%, respectively. This positive trend compared with baseline continued beyond 96 weeks of treatment. Improvements from baseline in pulmonary function occurred along with gains in height in the younger group (5.5% change) and in the older patient group (2.4% change) at 96 weeks. Changes in MVV occurred earlier within 24 weeks of treatment to approximately 15% over baseline. Model results based on data from all trials showed significant improvements in the rate of change in pulmonary function during 96 weeks on ERT, whereas little or no improvement was observed for the same time period prior to ERT. Thus, analysis of mean percent change data and longitudinal modeling both indicate that long-term ERT resulted in improvement in pulmonary function in MPS VI patients

Síndrome de DiGeorge: um relato de caso: DiGeorge's Syndrome: a case report

O presente artigo objetivou apresentar o caso clínico de uma paciente pediátrica diagnosticada com a síndrome de DiGeorge e que foi admitida no setor de Cardiologia Pediátrica para correção de malformação cardíaca. Este trabalho se trata de um estudo descritivo, do tipo relato de caso, que visou analisar as principais manifestações desse distúrbio genético, bem como suas abordagens diagnósticas e terapêuticas. A criança foi submetida à correção de defeito cardíaco característico da anomalia e evoluiu com parada cardiorrespiratória, prontamente revertida, e com crise convulsiva no pós-operatório. A anomalia possui espectro clínico diverso, com repercussões que impactam sobremaneira no equilíbrio eletrolítico e nos sistemas imunológico e cardiovascular, exigindo reconhecimento em tempo hábil e a adoção de condutas assertivas para reduzir a morbidade do portador

Reduced glucosylceramide in the mouse model of Fabry disease: correction by successful enzyme replacement therapy

Fabry disease is an X-linked lysosomal storage disease (LSD) caused by deficient activity of α-Galactosidase A (α-Gal A). As a result, glycosphingolipids, mainly globotriaosylceramide (Gb3), progressively accumulate in body fluids and tissues. Studies aiming at the identification of secondary lipid alterations in Fabry disease may be potentially useful for the monitorization of the response to enzyme replacement therapy (ERT) and development of future therapies. The focus of this study was to evaluate if α-Gal A deficiency has an effect on two key groups of molecules of sphingolipids metabolism: glucosylceramides (GlucCers) and ceramides (Cers). Studies performed in a mouse model of Fabry disease showed reduced level of GlucCer and normal level of Cer in plasma, liver, spleen, kidney and heart. Moreover, analysis of GlucCer isoforms in Fabry knockout mice showed that GlucCer isoforms are unequally reduced in different tissues of these animals. ERT had a specific effect on the liver's GlucCer levels of Fabry knockout mice, increasing hepatic GlucCer to the levels observed in wild type mice. In contrast to Fabry knockout mice, plasma of Fabry patients had normal GlucCer and Cer but an increased GlucCer/Cer ratio. This alteration showed a positive correlation with plasma globotriaosylsphingosine (lyso-Gb3) concentration. In conclusion, this work reveals novel secondary lipid imbalances caused by α-Gal A deficiency.FEDER funds through the Operational Competitiveness Programme—COMPETE and by National Funds through FCT—Fundação para a Ciência e a Tecnologia under the project FCOMP-01-0124-FEDER-022718 (PEst-C/SAU/LA0002/2011). The sponsors had no influence on the conception, study design, data collection, analysis or interpretation, manuscript writing as well as on the decision to submit the article for publication. R Quinta was supported by a fellowship from Fundação para a Ciência e Tecnologia (SFRH/BD/33447/2008). This work is part of the PhD thesis of R Quint

Synthesis and functionalization of Fe3O4@Au core-shell nanoparticles for the electrochemical detection of maize MON81O

International Conference on Electroanalysis, ESEAC 2014 (15ª. 2014. Malmö, Suecia). Poste