The Portugues General Practitioner Sentinel Network

Brief description of The Portuguese General Practitioner Sentinel Network with work examples as well as advantages in participating.N/

Two cases of late-onset Argininosuccinic aciduria with normal results at newborn screening

Argininosuccinic aciduria (ASA) is an autosomal recessive metabolic disorder caused by Argininosuccinate Lyase (ASL) deficiency, and it is the second most frequent urea cycle disorder, with an estimated frequency of 1:70 000. The human ASL gene is located on chromosome 7q11.21 and comprises 16 exons encoding a 464 amino acids long monomer. The enzyme is functional in a homotetrameric structure and is mainly expressed in the liver, although it can be found in several other tissues. The clinical presentation of ASA is very heterogeneous, ranging from asymptomatic to severe hyperammonemic neonatal-onset cases. Complex clinical phenotypes, with neurological deficits and hepatic complications adding to hyperammonemic episodes, are often observed. Biochemically, ASA is usually characterized by elevation of both citrulline and argininosuccinic acid in plasma and urine, but also at this level heterogeneity is observed, adding to a poor correlation found between residual enzymatic activity and the severity of the clinical phenotype. Newborn Screening (NBS) for ASA is widely established although some paradoxal results can be obtained due to the clinical and biochemical ASA heterogeneity: asymptomatic cases can be detected and, on the contrary, late-onset forms with important clinical manifestations observed since the first months of live can be missed due to normal biochemical results. ASA was included in the Portuguese NBS Program in 2005, based on elevated argininosuccinic acid blood levels. During these ten years of NBS two cases were identified and two other were missed. The missed cases were two brothers with a late-onset clinical form, which presented completely normal results at NBS. They are homozygous for R12Q mutation, which is a mutation reported to be associated with a mild clinical form of the disease and frequently found in late-onset ASA cases. Based on this finding it is important to keep in mind that a late-onset form of ASA should be considered for a child with clinical signs fitting this disease, even if NBS had a normal result

Tradução e gênero. Conversando com Luise von Flotow

This interview between Luise von Flotow and the guest editors was carried out online in March 2022. Flotow was the keynote speaker at the 9th IATIS Regional Workshop “Perspectives on Translation, Feminisms and Gender from Latin America,” held online in La Plata, Argentina, in 2020. This event, which gathered scholars mostly from Argentina and Brazil, aimed at engaging in fruitful dialogues between established and emerging paradigms in the field of feminist translation studies. It particularly intended to explore transnational perspectives within the field of feminist translation (studies). This conversation with Flotow, a founding and leading figure of the field, aims at pursuing this agenda further by disseminating her views on gender issues and translation, feminist translation, queer approaches to translation, transnational dialogues, and methodological insights. Esta entrevista entre Luise von Flotow y las editoras invitadas se llevó a cabo en línea en marzo de 2022. Flotow fue la oradora principal del 9th IATIS Regional Workshop “Perspectivas latinoamericanas sobre traducción, feminismos y género”, que tuvo lugar de manera virtual en la ciudad de La Plata, Argentina, en diciembre de 2020. Este foro, que reunió a especialistas principalmente de Argentina y Brasil, buscó instituir diálogos fructíferos entre paradigmas establecidos y emergentes en el campo de la traducción y de la traductología feministas. En particular, el coloquio buscó explorar perspectivas transnacionales en los ámbitos de la traducción feminista. Esta conversación con Flotow, una figura fundadora y referente del campo, se propone avanzar en esta agenda mediante la difusión de sus reflexiones sobre cuestiones de género y traducción, traducción feminista, enfoques queer de la traducción, diálogos transnacionales y aspectos metodológicos.Esta entrevista entre Luise von Flotow e as editoras convidadas foi realizada online em março de 2022. Flotow proferiu a conferência de abertura do 9º Workshop Regional do IATIS “Perspectivas latino-americanas sobre tradução, feminismos e gênero”, realizado online em La Plata, Argentina, em 2020. Este evento, que reuniu pesquisadores e pesquisadoras principalmente da Argentina e do Brasil, teve por objetivo estabelecer diálogos frutíferos entre paradigmas estabelecidos e emergentes no campo dos estudos feministas da tradução. Pretendia particularmente explorar as perspectivas transnacionais dos estudos da tradução feminista. Esta conversa com Flotow, uma figura fundadora e expoente da área, visa avançar essa proposta, compartilhando seus pontos de vista sobre questões de gênero e tradução, tradução feminista, abordagens queer à tradução, diálogos transnacionais e aspectos metodológicos

Microplastics effects in Scrobicularia plana

One of the most common plastics in the marine environment is polystyrene (PS) that can be broken down to micro sized particles. Marine organisms are vulnerable to the exposure to microplastics. This study assesses the effects of PS microplastics in tissues of the clam Scrobicularia plana. Clams were exposed to 1mgL-1(20μm) for 14days, followed by 7days of depuration. A qualitative analysis by infrared spectroscopy in diffuse reflectance mode period detected the presence of microplastics in clam tissues upon exposure, which were not eliminated after depuration. The effects of microplastics were assessed by a battery of biomarkers and results revealed that microplastics induce effects on antioxidant capacity, DNA damage, neurotoxicity and oxidative damage. S. plana is a significant target to assess the environmental risk of PS microplastics.info:eu-repo/semantics/publishedVersio

Bicultural Competence and the Latino 2.5 Generation: The Acculturative Advantages and Challenges of Having One Foreign-Born and One U.S.-Born Parent

The 2.5 generation refers to individuals who have one parent born in the United States and one born in another country. The presence of both native-born and foreign-born parents has the potential to enhance bicultural adaptation. Across two studies with Latino young adults, we examine the extent to which the 2.5 generation is distinct from members of other generations with regard to cultural orientation, acculturative stress, and parent ethnic socialization. Results suggest that the 2.5-generation individuals report greater native cultural orientation, ethnic identity, and parental socialization compared with third-generation individuals, along with greater American orientation than first-generation individuals. The 2.5 generation also reports less language use and more acculturative stress due to Spanish competency pressures than firstand second-generation individuals. These results demonstrate that the 2.5-generation individuals may have some bicultural advantages compared with third-generation individuals; however, they may also experience similar challenges with regard to language maintenance

Bicultural Competence and the Latino 2.5 Generation: The Acculturative Advantages and Challenges of Having One Foreign-Born and One U.S.-Born Parent

The 2.5 generation refers to individuals who have one parent born in the United States and one born in another country. The presence of both native-born and foreign-born parents has the potential to enhance bicultural adaptation. Across two studies with Latino young adults, we examine the extent to which the 2.5 generation is distinct from members of other generations with regard to cultural orientation, acculturative stress, and parent ethnic socialization. Results suggest that the 2.5-generation individuals report greater native cultural orientation, ethnic identity, and parental socialization compared with third-generation individuals, along with greater American orientation than first-generation individuals. The 2.5 generation also reports less language use and more acculturative stress due to Spanish competency pressures than firstand second-generation individuals. These results demonstrate that the 2.5-generation individuals may have some bicultural advantages compared with third-generation individuals; however, they may also experience similar challenges with regard to language maintenance

Programa Nacional de Diagnóstico Precoce em Portugal- Casuística de 2011

O Programa Nacional de Diagnóstico Precoce (PNDP) visa identificar doenças nas primeiras semanas de vida do bebé de forma a possibilitar uma intervenção precoce e a impedir a ocorrência de atraso mental, doença grave irreversível ou morte da criança. O PNDP iniciou-se em 1979 com o rastreio da fenilcetonúria tendo-se implementado em 1981 o rastreio do hipotiroidismo congénito. As novas tecnologias de espectrometria de massa, permitindo a análise simultânea de vários parâmetros numa só amostra de sangue, possibilitaram, a partir de 2004, o aumento das doenças rastreadas até às atuais 25 (24 doenças hereditárias do metabolismo e o hipotiroidismo congénito). O rastreio é feito sobre o sangue colhido por picada no pé do bebé, entre o 3º e o 6º dia de vida, para uma ficha com papel de filtro adequado, sendo a totalidade das análises efetuadas na Unidade de Rastreio Neonatal Metabolismo e Genética do INSA. A taxa de cobertura do PNDP é 100% dos recém - nascidos, sendo o tempo médio de início de tratamento de 9,87 dias. Em Portugal, durante o ano de 2011, foram rastreados 97.116 recém-nascidos tendo-se identificado 44 casos de Hipotiroidismo Congénito (1/2.207) e 31 casos de doenças hereditárias do metabolismo (1/3.133). Os programas de rastreio neonatal são sistemas dinâmicos que devem ser continuamente avaliados e atualizados. Nesta conformidade, há duas doenças cuja integração no Programa Nacional de Diagnóstico Precoce, deve ser considerada e avaliada, atendendo à realidade atual em termos demográficos e de tratamento efetivo - a fibrose quística e a anemia falciforme (drepanocitose). Serão assim integradas no projeto de desenvolvimento futuro do rastreio neonatal em Portugal

Aplicação dos marcadores IRT/PAP/IRT no rastreio neonatal da fibrose quística

A Fibrose Quística (FQ) é uma doença genética, com transmissão autossómica recessiva. Bioquimicamente deve-se à deficiência na proteína Cystic Fibrosis Transmembrane Condutance Regulator que é codificada pelo gene CFTR, localizado no cromossoma 7. Estão descritas cerca de 2000 variantes genéticas associadas a esta doença. Iniciou-se no final de 2013 um estudo piloto integrado no Programa Nacional de Diagnóstico Precoce (PNDP), que incluiu 80,000 recém-nascidos (RN). O aumento da concentração sanguínea da tripsina imunoreactiva (IRT) nos primeiros dias de vida dos RN com FQ possibilita o rastreio neonatal desta doença. No entanto, apesar de uma boa sensibilidade (95%), o IRT não é um marcador específico (34-75%) para a FQ, e um rastreio baseado unicamente neste marcador tem um número elevado de falsos positivos. Por esta razão, têm sido propostos vários algoritmos de rastreio, incluindo outros marcadores bioquímicos como a Proteína Associada à Pancreatite (PAP). Neste estudo, o algoritmo de rastreio utilizado baseia-se na determinação do IRT / PAP / IRT em sangue colhido em papel de filtro, sendo a amostra de sangue a mesma colhida para as restantes doenças rastreadas. Neste estudo foram identificadas 680 amostras com valor elevado de IRT ao rastreio, mas apenas em 272 casos foram solicitadas novas amostras por apresentarem também aumento de PAP. Esta estratégia reduziu significativamente os pedidos de segunda amostra de sangue. Foram diagnosticados neste estudo 11 doentes, o que implica uma prevalência ao nascimento de aproximadamente 1:7,200, no entanto este estudo será alargado a mais 80,000 RN para estabelecermos a real prevalência desta patologia na nossa população

3-Methylcrotonyl CoA Carboxylase Deficiency: Disorder or Just a Biochemical Phenotype?

Introduction: 3-methylcrotonyl-CoA carboxylase deficiency (MCCD) was considered extremely rare before newborn screening (NBS) was undertaken but is now found in a number of asymptomatic babies or sometimes their mothers. This disorder of leucine metabolism, is the commonest organic aciduria found by screening, with a incidence of about 1:32 392 in our country. The clinical phenotype has been shown to vary considerably, ranging from entirely asymptomatic to death in infancy. A review of the literature on 37 individuals indicates that only 27% developed normally and stayed completely asymptomatic. Approximately 30% were reported to suffer from muscular hypotonia and psychomotor retardation, and almost half suffer from various other neurological symptoms. Even a lethality of 11% was observed. The metabolic phenotype characterizing MCCD is the elevated excretion of the diagnostic compounds 3-methylcrotonylglycine and 3-hydroxyisovaleric acid, and the presence of abnormally elevated blood levels of 3-hydroxyisovalerylcarnitine (C5-OH), as determined by tandem mass spectrometry (MS/MS). Patient and methods: The authors present a symptomatic case with an increase of C5-OH in the acylcarnitine profile who have a developmental delay. Blood spot samples from newborns are collected between day 3 and 6 in Watman 903 filter paper. Acylcarnitines in samples are analysed by MS/MS. Genes MCCA and MCCB that encodes the enzyme 3-MCC were studied by reported methods. Results: The molecular study has allowed the identification of the compound heterozygous in this patient: the frameshift mutation p.S173FfsX25 and the missense mutation p.V339M. Both mutations are described in the literature. Discussion: The newborn screening identification of a patient which developed symptoms seems to indicate that this disease should be included in NBS programs. More studies are needed to find genetic and/or biochemical markers that explain why a relatively small number of individuals are at risk of developing a severe disease phenotype. Another important reason to include MCCD in our panel is that other disorders are also detected by the marker C5OH; for example deficiencies of holocarboxylase synthetase, and 3-hydroxy- 3-methylglutaryl-CoA lyase

Newborn screening for urea cycle disorders in Portugal

Os défices do ciclo da ureia são um grupo de doenças hereditárias do metabolismo caracterizadas fundamentalmente por uma acumulação de amónia. Clinicamente o espectro é muito alargado, com formas de apresentação no período neonatal até situações mais moderadas de apresentação tardia em adultos. O tratamento é fundamentalmente de base nutricional e traduz-se numa redução significativa da mortalidade e morbilidade. Com a introdução da espectrometria de massa nos laboratórios de rastreio neonatal em meados dos anos 90, passou a ser possível quantificar alguns intermediários do ciclo, o que associado à existência de um intervalo livre e um tratamento eficaz, permitiu o rastreio de algumas das doenças deste grupo. Em 2004 iniciou-se em Portugal o rastreio dos défices do ciclo da ureia, tendo-se rastreado até ao presente, 988 687 recém-nascidos e identificado 19 casos positivos. Recentes desenvolvimentos técnicos vieram possibilitar a quantificação de novos marcadores, mais concretamente do ácido orótico, o que abre a possibilidade de rastrear o défice em ornitina transcarbamilase, o défice do ciclo da ureia mais frequente. Os autores apresentam a situação atual do rastreio dos défices do ciclo da ureia e as perspetivas em virtude dos novos desenvolvimentos técnicos.Urea cycle disorders (UCDs) are a group of inborn errors of metabolism characterized by ammonia accumulation. The clinical spectrum is very heterogeneous and ranges from neonatal presentations to almost asymptomatic adults. Treatment is mainly based on a protein-restricted diet and results in a significant decrease of mortality and morbidity. The introduction of tandem mass spectrometry-based techniques in newborn screening laboratories in the middle 90’s has allowed to detect and quantify several intermediates of the cycle, and this, alongside with the existence of a symptom-free interval after birth and effective treatment, allowed to screen for some UCDs. Since 2004, the Portuguese newborn screening program for UCDs has analyzed 988 687 newborns and 19 positive cases were detected. Recent technical developments allow quantifying other UCDs markers on Guthrie cards, more precisely orotic acid which opens the possibility to screen for ornitine transcarbamylase deficiency, the most common UCD. The authors will review the current status of the newborn screening for UCDs and present future perspectives.Parte deste trabalho foi desenvolvido no âmbito do projeto “Atualização tecnológica do Programa Nacional de Diagnóstico Precoce” (Operação NORTE–07-0162-FEDER-000142), financiado pelo programa ON2–QREN