Browsing by Author "Fraga, J."
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- Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disordersPublication . Fernández-Marmiesse, A.; Morey, M.; Pineda, M.; Eiris, J.; Couce, M.; Castro-Gago, M.; Fraga, J.; Lacerda, L.; Gouveia, S.; Pérez-Poyato, M.; Armstrong, J.; Castiñeiras, D.; Cocho, J.BACKGROUND: With over 50 different disorders and a combined incidence of up to 1/3000 births, lysosomal storage diseases (LSDs) constitute a major public health problem and place an enormous burden on affected individuals and their families. Many factors make LSD diagnosis difficult, including phenotype and penetrance variability, shared signs and symptoms, and problems inherent to biochemical diagnosis. Developing a powerful diagnostic tool could mitigate the protracted diagnostic process for these families, lead to better outcomes for current and proposed therapies, and provide the basis for more appropriate genetic counseling. METHODS: We have designed a targeted resequencing assay for the simultaneous testing of 57 lysosomal genes, using in-solution capture as the enrichment method and two different sequencing platforms. A total of 84 patients with high to moderate-or low suspicion index for LSD were enrolled in different centers in Spain and Portugal, including 18 positive controls. RESULTS: We correctly diagnosed 18 positive blinded controls, provided genetic diagnosis to 25 potential LSD patients, and ended with 18 diagnostic odysseys. CONCLUSION: We report the assessment of a next-generation-sequencing-based approach as an accessory tool in the diagnosis of LSDs, a group of disorders which have overlapping clinical profiles and genetic heterogeneity. We have also identified and quantified the strengths and limitations of next generation sequencing (NGS) technology applied to diagnosis.
- Miosite orbitária numa criançaPublication . Fraga, J.; Sá, A.; Cândido, C.; Pinto, J.; Dias, F.Introdução: A doença inflamatória orbitária caracteriza-se por um processo inflamatório, de etiologia desconhecida, que pode atingir qualquer estrutura da órbita. Apresentamos um caso clínico da forma que envolve os músculos extraoculares (miosite orbitária). Caso clínico: Criança do sexo masculino com nove anos de idade, sem antecedentes patológicos de relevo, que iniciou subitamente dor ocular à direita, acompanhada de edema palpebral homolateral. À observação, apresentava proptose, edema palpebral moderado com rubor local, limitação da elevação da pálpebra e da elevação e abdução do olho direito, com diplopia. A investigação efectuada sugeriu o diagnóstico de miosite orbitária, tendo iniciado terapêutica com corticóide sistémico com resolução do quadro. Discussão: O presente caso descreve uma entidade nosológica rara em idade pediátrica, habitualmente benigna, mas que se não reconhecida e tratada precocemente, pode originar sequelas da mobilidade ocular. ABSTRACT Background: Orbital inflammatory disease is characterized by an inflammatory process of unknown etiology, which may affect any structure of the orbit. We describe a case report of inflammation of the extraocular muscles (orbital myositis). Case report: A previously healthy nine year-old male, with negative paste medical history, presented with right eye pain and homolateral eyelid swelling of sudden onset. On physical examination there was proptosis, eyelid edema with moderate local redness, and diplopia with limitation in the elevation of the eyelid and of abduction and elevation of the eye. The investigation suggested the diagnosis of orbital myositis. Intravenous corticosteroid therapy was started with clinical improvement. Discussion: This case report reports a rare, usually benign, entity in children, which if not early recognized and treated may cause persistent eye motility dysfunction.
- Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: regional experience and high incidence of carnitine deficiencyPublication . Couce, M.; Sánchez-Pintos, P.; Diogo, L.; Leão-Teles, E.; Martins, E.; Santos, H.; Amor Bueno, M.; Delgado-Pecellín, C.; Castiñeiras, D.; Cocho, J.; García-Villoria, J.; Ribes, A.; Fraga, J.; Rocha, HBackground Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common inherited defect in the mitochondrial fatty acid oxidation pathway, resulting in significant morbidity and mortality in undiagnosed patients. Newborn screening (NBS) has considerably improved MCADD outcome, but the risk of complication remains in some patients. The aim of this study was to evaluate the relationship between genotype, biochemical parameters and clinical data at diagnosis and during follow-up, in order to optimize monitoring of these patients. Methods We carried out a multicenter study in southwest Europe, of MCADD patients detected by NBS. Evaluated NBS data included free carnitine (C0) and the acylcarnitines C8, C10, C10:1 together with C8/C2 and C8/C10 ratios, clinical presentation parameters and genotype, in 45 patients. Follow-up data included C0 levels, duration of carnitine supplementation and occurrence of metabolic crises. Results C8/C2 ratio and C8 were the most accurate biomarkers of MCADD in NBS. We found a high number of patients homozygous for the prevalent c.985A > G mutation (75%). Moreover, in these patients C8, C8/C10 and C8/C2 were higher than in patients with other genotypes, while median value of C0 was significantly lower (23 μmol/L vs 36 μmol/L). The average follow-up period was 43 months. To keep carnitine levels within the normal range, carnitine supplementation was required in 82% of patients, and for a longer period in patients homozygotes for the c.985A>G mutation than in patients with other genotypes (average 31 vs 18 months). Even with treatment, median C0 levels remained lower in homozygous patients than in those with other genotypes (14 μmol/L vs 22 μmol/L). Two patients died and another three suffered a metabolic crisis, all of whom were homozygous for the c.985 A>G mutation. Conclusions Our data show a direct association between homozygosity for c.985A>G and lower carnitine values at diagnosis, and a higher dose of carnitine supplementation for maintenance within the normal range. This study contributes to a better understanding of the relationship between genotype and phenotype in newborn patients with MCADD detected through screening which could be useful in improving follow-up strategies and clinical outcome.
- Parotidite recorrente juvenil… nem sempre é o que parecePublication . Sá, A.; Fraga, J.; Costa, A.M.; Dias, F.; Brito, I.RESUMO Introdução: A parotidite recorrente juvenil (PRJ) é uma inflamação recidivante idiopática da glândula parótida, geralmente associada a sialectasia não-obstrutiva. A síndrome de Sjögren (SS), rara em idade pediátrica, pode apresentar-se nesta faixa etária sob a forma de parotidites de repetição. Caso clínico: Menina, de 13 anos, que no quarto episódio de tumefação e dor parotídea, iniciou investigação etiológica que revelou glândulas parótidas ecograficamente com textura heterogénea e múltiplas calcificações punctiformes, título ANA elevado (1:1280) com padrão mosqueado, anticorpos Anti-SSA e Anti-SSB positivos, assim como o fator reumatóide, hiper-gamaglobulinémia e elevação da imunoglobulina G. Verificou-se, também, elevação da creatinofosfoquinase, da transamínase glutâmico-oxalacética e da transamínase glutâmico-pirúvica. A biópsia das glândulas salivares minor foi compatível com diagnóstico de SS. Iniciou terapêutica com hidroxicloroquina e corticóide oral em baixa dose com resposta clínica favorável. Discussão/Conclusão: A idade de aparecimento da tumefação parotídea ajuda no diagnóstico diferencial entre PRJ idiopática e uma etiologia inß amatória crónica. O envolvimento muscular está descrito no SS primário e tem um espectro clínico e patológico variado, sendo que a miosite subclínica surge numa percentagem que varia entre os 5% e os 37%.
- Prevenção de acidentes: o que sabem os paisPublication . Costa, A.; Sá, A.; Fraga, J.; Dias, F.; Serafim, M.J.Introdução: Os acidentes domésticos e rodoviários são causa frequente de morbilidade e mortalidade infantil. Objectivo: avaliar o conhecimento das normas de segurança infantil por parte dos pais, tendo em conta o grau de habilitações académicas (Ensino Básico (B), Ensino Secundário (S), Ensino Superior (SU)). Material e métodos: Estudo transversal com aplicação de um inquérito aos pais de crianças entre os 9 meses-6 anos. Na análise estatística utilizou-se o teste χ2 (p<0,05), recorrendo ao programa SPSS versão17.0. Resultados: Foram recolhidos 281 inquéritos (46% SU). As principais fontes de informação sobre prevenção de acidentes foram os meios de comunicação (86,7%) e o médico (69,5%). Relativamente às medidas de segurança gerais da habitação salientam-se os seguintes resultados: 40,2% sem trincos de segurança nas varandas ou janelas (B 26,8%, S 36,8%, SU 48,5%, p=0,014); ausência de protecção nas escadas em 47,5% (B 17,9%, S 44,4%, SU 59,5%, p=0,000) e nas lareiras 28,1%; 33,1% sem protecções de tomadas eléctricas e 70,2% sem protecções de esquinas. Na cozinha, 30,2% dos pais deixavam as crianças sozinhas; 22,8% cozinhavam com crianças ao colo; 49,5% não guardavam em local inacessível os detergentes e 8,5% mudavam a embalagem original (B19,6%, S11,6%, SU1,5%, p=0,000). O uso de andarilho registou-se em 34,2% dos inquéritos. No automóvel, 32,4% dos pais transportaram o filho ao colo. Conclusões: Verifica-se que muitos pais não cumprem as regras básicas de segurança e não adoptam estratégias de prevenção de acidentes domésticos. Considerando os diferentes níveis de educação, na generalidade, os comportamentos inadequados são comuns a todos os grupos. Aos profissionais de saúde cabe orientar e alertar os pais na mudança de atitudes e comportamentos. ABSTRACT Introduction: Home and traffic accidents are a frequent cause of child morbidity and mortality. Objective: To assess parents’ knowledge of child safety standards, taking into account their level of education (Basic (B), Secondary (S), Academic degree (A)). Materials and methods: Cross-sectional study with application of a questionnaire to parents of children aged 9 months to 6 years. The χ2 test (p <0.05) was used for the statistical analysis, using the SPSS version 17.0. Results: A total of 281 inquiries were collected (46% A). The main sources of information about accident prevention were the media (86,7%) and the doctor (69,5%). At home, 40,2% of the houses did not have safety latches on the balconies or windows (B 26,8%, S 36,8%, A 48,5%, p=0,014); 47,5% of those with stairs had no protection (B 17,9%, S 44,4%, A 59,5%, p=0,000), as well as 28,1% of those with fi replace; 33,1% had no protection for electrical outlets, or corners (70,2%). In the kitchen, 30,2% of the parents left their children alone; 22,8% cooked with children in their arms; 49,5% didn’t keep detergents in an inaccessible place and 8,5% changed the original packing (B 19,6%, S 11,6%, A 1,5%, p=0,000). 34,2% of the children used walkers. 32,4% of the parents carried the child on their lap in the car. Conclusions: We conclude that many parents are not aware of basic safety rules and do not implement measures to prevent home accidents. Considering the different level of education, in the generality, inappropriate attitudes were found in all groups. Health professionals should guide and alert parents to change attitudes and behaviours.