Microcephaly in South Brazil: Are cases of Congenital Zika Syndrome increasing in recent years?

Northeast Brazil was the first region to detect a significant increase in babies born with microcephaly associated with prenatal zika virus infection in 2015. Rio Grande do Sul (RS) state was less impacted due to the temperate climate preventing the spread of the vector. This study investigated the prevalence and etiology of congenital microcephaly in RS in two different periods. This cross-sectional descriptive study included all live births with congenital microcephaly in RS from 2015 to 2022. Cases were divided into two groups: P1 "outbreak" (2015-16); and P2 "endemic" (2017-22). There were 58 cases of microcephaly (3.8/10,000) in P1 and 148 (1.97/10,000) in P2. Congenital Zika Virus infection was the etiology in 5.2% (n=3) in P1 and 6.7% (n=10) in P2. In conclusion, although the ZIKV outbreak in Brazil has receded, RS remains an area of concern, with a possible slight increase of live births with microcephaly secondary to ZIKV prenatal infection relative to the number of cases due to congenital infections. The broader distribution of the vector Aedes aegypti with warmer temperatures in our state might be linked to the increase in recent years. This study can be an alert to other regions of temperate or subtropical climates.

Course for the qualification of nurses in the care of children with genetic diseases: an experience report.

OBJECTIVE: To describe the experience of developing and operating an extension course to qualify nurses in the care of children with genetic diseases. METHOD: An experience report about the conduction of a university extension course with eight participants, developed at a public university in southern Brazil. It was a face-to-face course in November 2019. RESULTS: The course covered the following themes: introduction to Genetics in Nursing; rare diseases; inborn errors of metabolism; Neonatal Screening Program; and microcephaly. The content was developed through theoretical aspects, presentation of clinical cases, practical activities, and realistic simulation. CONCLUSION: The extension course provided knowledge to nurses, who develop their functions as team leaders, enabling professional development and the promotion of information on the topic, which corroborates the objectives of the Nursing Now campaign.

Course for qualification of nurses in the care of children with genetic diseases: experience report / Curso de calificación de enfermeras en el cuidado de niños con enfermedades genéticas: informe de experiencia / Curso para qualificação de enfermeiros no cuidado de crianças com doenças genéticas: relato de experiência

ABSTRACTObjective: To describe the experience of developing and operating an extension course to qualify nurses in caring for children with genetic diseases.Method: Experience report on the realization of a university extension course had eight participants, developed at a public university in southern Brazil. The course took place in person, in November 2019.Results: The course covered the following themes: introduction to genetics in nursing; rare diseases; innate errors of metabolism; Neonatal Screening Program; and microcephaly. The content was developed through theoretical aspects, presentation of clinical cases, practical activities and realistic simulation.Conclusion: The extension course provided knowledge to nurses, who develop their functions as team leaders, allowing professional development and the dissemination of information on the topic, which corroborates the objectives of the Nursing Now campaign.Keywords: Genetic diseases, inborn. Pediatrics. Education, nursing. High fidelity simulation training.

RESUMENObjetivo: Describir la experiencia de desarrollo y operacionalización de un curso de extensión para calificar enfermeras en el cuidado de niños con enfermedades genéticas.Método: Informe de experiencia sobre la realización de un curso de extensión universitaria con ocho participantes, desarrollado en una universidad pública en el sur de Brasil. El curso tuvo lugar en persona, en noviembre de 2019.Resultados: El curso cubrió los siguientes temas: introducción a la genética en enfermería; enfermedades raras; errores innatos del metabolismo; Programa de detección neonatal; y microcefalia. El contenido se desarrolló mediante el desarrollo de aspectos teóricos, la presentación de casos clínicos, actividades prácticas y simulación realista.Conclusión: El curso de extensión proporcionó conocimiento a los enfermeros, quienes desarrollan sus roles como líderes de equipo, permitiendo el desarrollo profesional y la difusión de información sobre el tema, lo que corrobora los objetivos de la campaña Nursing Now.Palavras clave: Enfermedades genéticas congénitas. Pediatría. Educación en enfermería. Enseñanza mediante simulación de alta fidelidad.

RESUMOObjetivo: Descrever a experiência de desenvolvimento e operacionalização de um curso de extensão para qualificar enfermeiros no cuidado de crianças com doenças genéticas.Método: Relato de experiência sobre a realização de um curso de extensão universitária com oito participantes, desenvolvido em uma universidade pública no sul do Brasil. O curso foi realizado na modalidade presencial, em novembro de 2019.Resultados: O curso contemplou os seguintes temas: introdução à genética na enfermagem, doenças raras, erros inatos do metabolismo, Programa de Triagem Neonatal e microcefalia. O conteúdo foi desenvolvido por meio do desenvolvimento dos aspectos teóricos, apresentação de casos clínicos, atividades práticas e simulação realística.Conclusão: O curso de extensão proporcionou conhecimento aos enfermeiros, que desenvolvem suas funções como líderes de equipe, permitindo o desenvolvimento profissional e a disseminação de informações sobre o tema, o que corrobora os objetivos da campanha Nursing Now. Palavras-chave: Doenças genéticas inatas. Pediatria. Educação em enfermagem. Treinamento com simulação de alta fidelidade.

Course for the qualification of nurses in the care of children with genetic diseases: an experience report / Curso de calificación de enfermeras en el cuidado de niños con enfermedades genéticas: informe de experiencia / Curso para qualificação de enfermeiros no cuidado de crianças com doenças genéticas: relato de experiência

ABSTRACT Objective To describe the experience of developing and operating an extension course to qualify nurses in the care of children with genetic diseases. Method An experience report about the conduction of a university extension course with eight participants, developed at a public university in southern Brazil. It was a face-to-face course in November 2019. Results The course covered the following themes: introduction to Genetics in Nursing; rare diseases; inborn errors of metabolism; Neonatal Screening Program; and microcephaly. The content was developed through theoretical aspects, presentation of clinical cases, practical activities, and realistic simulation. Conclusion The extension course provided knowledge to nurses, who develop their functions as team leaders, enabling professional development and the promotion of information on the topic, which corroborates the objectives of the Nursing Now campaign.

RESUMEN Objetivo Describir la experiencia de desarrollo y operacionalización de un curso de extensión para calificar enfermeras en el cuidado de niños con enfermedades genéticas. Método Informe de experiencia sobre la realización de un curso de extensión universitaria con ocho participantes, desarrollado en una universidad pública en el sur de Brasil. El curso tuvo lugar en persona, en noviembre de 2019. Resultados El curso cubrió los siguientes temas: introducción a la Genética en Enfermería; enfermedades poco comunes; errores innatos del metabolismo; Programa de detección neonatal; y microcefalia. El contenido se desarrolló mediante el desarrollo de aspectos teóricos, la presentación de casos clínicos, actividades prácticas y simulación realista. Conclusión El curso de extensión proporcionó conocimiento a las enfermeras, quienes desarrollan sus roles como líderes de equipo, permitiendo el desarrollo profesional y la difusión de información sobre el tema, lo que corrobora los objetivos de la campaña Nursing Now.

RESUMO Objetivo Descrever a experiência de desenvolvimento e operacionalização de um curso de extensão para qualificar enfermeiros no cuidado de crianças com doenças genéticas. Método Relato de experiência sobre a realização de um curso de extensão universitária com oito participantes, desenvolvido em uma universidade pública no sul do Brasil. O curso foi realizado na modalidade presencial, em novembro de 2019. Resultados O curso contemplou os seguintes temas: introdução à genética na enfermagem, doenças raras, erros inatos do metabolismo, Programa de Triagem Neonatal e microcefalia. O conteúdo foi desenvolvido por meio do desenvolvimento dos aspectos teóricos, apresentação de casos clínicos, atividades práticas e simulação realística. Conclusão O curso de extensão proporcionou conhecimento aos enfermeiros, que desenvolvem suas funções como líderes de equipe, permitindo o desenvolvimento profissional e a disseminação de informações sobre o tema, o que corrobora os objetivos da campanha Nursing Now.

Contato pele a pele e aleitamento materno: experiências de puérperas / Contacto piel con piel y lactancia materna: experiencias de mujeres posparto / Skin-to-skin contact and breastfeeding: experiences of puerperalmothers

Objetivo: Descrever as experiências de puérperas quanto ao contato pele a pele com o recém-nascido, realizado na primeira hora de vida e o início do aleitamento materno. Método: Trata-se de um estudo exploratório-descritivo, realizado com abordagem qualitativa. A pesquisa foi desenvolvida com puérperas no Alojamento Conjunto de um hospital privado. Para a coleta dos dados foi utilizada a técnica de entrevista semiestruturada. As informações foram submetidas à técnica de análise de conteúdo do tipo temática. Resultados: Foram elaboradas duas categorias: Contato pele a pele, na primeira hora de vida e os sentimentos vivenciados e Vivenciando o início do aleitamento materno. Observou-se que o contato pele a pele não fora realizado, conforme preconizado, mas, apesar disso, as participantes consideraram esse momento como importante, para auxiliar no início do aleitamento materno, pois se sentiram mais confiantes. Conclusão: Identificou-se que a instituição ainda utiliza um modelo intervencionista. Dessa forma, esta pesquisa foi relevante, pois poderá contribuir para a reflexão dos profissionais em relação aos cuidados prestados ao binômio mãe-bebê, possibilitando a qualificação das práticas do contato pele a pele e do aleitamento materno na primeira hora de vida. (AU)

Objective: To describe the skin-to-skin contact experiences of puerperal mothers with their newborn in the first hour of life and the beginning of breastfeeding. Method: This is an exploratory-descriptive study, conducted with a qualitative approach. The research was developed with puerperal mothers in join accommodation of a private hospital. To collect the information, the semi-structured interview technique was used. The information was submitted to the thematic content analysis technique. Results: Two categories were elaborated: Skin-to-skin contact in the first hour of life and the feelings they had and The experiences in the beginning of breastfeeding. It was observed that the skin-to-skin contact was not performed as recommended, but despite this, the participants considered this moment as important to help in the beginning of breastfeeding, as they felt more confident. Conclusion: It was identified that the institution still uses an interventionist model. Thus, this research was relevant, as it may contribute to the professionals' reflection on the care provided to the mother-baby binomial, enabling the qualification of skin-to-skin contact practices and breastfeeding in the first hour of life.(AU)

Objetivo: describir las experiencias de las mujeres posparto con respecto al contacto piel con piel con el recién nacido en la primera hora de vida y el comienzo de la lactancia. Método: este es un estudio exploratorio descriptivo, realizado con un enfoque cualitativo. La investigación se desarrolló con madres en el alojamiento conjunto de un hospital privado. Para recopilar la información, se utilizó la técnica de entrevista semiestructurada. La información se envió a la técnica de análisis de contenido temático. Resultados: se elaboraron dos categorías: Contacto piel con piel en la primera hora de vida y los sentimientos experimentados y experimentando el comienzo de la lactancia materna. Se observó que el contacto piel con piel no se realizó según lo recomendado, pero a pesar de esto, los participantes consideraron que este momento era importante para ayudar al comienzo de la lactancia, ya que se sentían más seguros. Conclusión: se identificó que la institución aún utiliza un modelo intervencionista. Por lo tanto, esta investigación fue relevante porque puede contribuir a la reflexión de los profesionales con respecto a la atención brindada al binomio madre-bebé, permitiendo la calificación de las prácticas de contacto piel con piel y lactancia materna en la primera hora de vida.(AU)

Vivências paternas na realização da posição canguru com recém-nascidos de baixo peso / Fathers' experiences using the kangaroo position with low-birth-weight infants / Experiencias paternas en la realización de la posición canguro con recién nacidos de bajo peso

Enquadramento: A posição canguru consiste em manter o recém-nascido em contacto pele a pele com mãe, pai ou cuidador eleito pela família. Os seus benefícios envolvem melhoria clínica e ganho de peso do recém-nascido. Objetivo: Descrever a vivência paterna durante a realização da posição canguru com o seu recém-nascido de baixo peso. Metodologia: Pesquisa de caráter exploratório-descritivo, com abordagem qualitativa, realizada em neonatologia, na região sul do Brasil. As informações foram colhidas por meio de entrevistas semiestruturadas e submetidas à análise de conteúdo temática. Resultados: Participaram 5 pais. Foram construídas 3 categorias, que contemplaram a ambivalência de sentimentos; as facilidades e as dificuldades vivenciadas; e o fortalecimento do vínculo pai-filho. Conclusão: É possível transcender os resultados deste estudo e pensar na posição canguru como uma estratégia para o estímulo da interação e do vínculo entre pai e filho, pode efetivamente ser o desencadeador para o desenvolvimento da paternidade.

Background: The kangaroo position consists of keeping the newborn in skin-to-skin contact with the mother, father, or caregiver elected by the family. Its benefits include the newborn's clinical improvement and weight gain. Objective: To describe the fathers' experiences using the kangaroo position with their low-birth-weight newborns. Methods: A descriptive exploratory research, with a qualitative approach, was conducted in a neonatal unit, in southern Brazil. Data were collected through semi-structured interviews, and a thematic content analysis was carried out. Results: Five fathers participated in the study, from which three categories resulted: the ambivalence of feelings; the ease and difficulty experienced; and the strengthening of the father-child bond. Conclusion: It is possible to go beyond the results of this study and consider the kangaroo position as a strategy to stimulate the father-child interaction and bonding, while effectively acting as a trigger for the development of fatherhood.

Marco contextual: La posición canguro consiste en mantener al recién nacido en contacto piel a piel con la madre, el padre o el cuidador elegido por la familia. Sus beneficios implican una mejora clínica y el aumento de peso del recién nacido. Objetivo: Describir la experiencia paterna durante la realización de la posición canguro con su recién nacido de bajo peso. Metodología: Investigación de carácter exploratorio-descriptivo, con un enfoque cualitativo, realizada en neonatología, en la región sur de Brasil. La información se recopiló mediante entrevistas semiestructuradas y se sometió a un análisis de contenido temático. Resultados: Cinco padres participaron. Se construyeron tres categorías, que contemplaban la ambivalencia de los sentimientos; las facilidades y las dificultades experimentadas, y el fortalecimiento del vínculo padre-hijo. Conclusión: Es posible trascender los resultados de este estudio y pensar en la posición canguro como una estrategia para estimular la interacción y el vínculo entre padre e hijo, puede ser efectivamente el detonante para el desarrollo de la paternidad.

Prevalence and causes of congenital microcephaly in the absence of a Zika virus outbreak in southern Brazil / Prevalência e causas da microcefalia congênita sem a presença do surto do vírus Zika no Sul do Brasil

Abstract Objective: The aim of this study was to identify the causes of congenital microcephaly in Rio Grande do Sul, a state in southern Brazil, where no ZIKV outbreak was detected, from December 2015 to December 2016, which was the period when ZIKV infection was at its peak in northeast Brazil. Methods: This was a cross-sectional study where all notifications of congenital microcephaly in the state of Rio Grande do Sul were included for analysis. Evaluation of cases followed the guidelines of the Brazilian Ministry of Health. Dysmorphological and neurological evaluations were performed by a specialized team, and genetic tests and neuroimaging were performed when clinically indicated. STORCH infections were diagnosed using standard tests. ZIKV infection was diagnosed through maternal serum RT-PCR and/or neuroimaging associated with clinical/epidemiological criteria. Results: From 153 744 registered live births in the study period, 148 cases were notified, but 90 (60.8%) of those were later excluded as "non-confirmed" microcephaly. In the 58 confirmed cases of microcephaly (prevalence = 3.8/10 000 live births), congenital infections (syphilis, toxoplasmosis, cytomegalovirus, and ZIKV) constituted the predominant etiology (50.0%), followed by isolated CNS (15.5%), and genetic syndromes (10.3%). Congenital ZIKV syndrome (CZS) with typical phenotype was diagnosed in three cases (5.2% of all confirmed microcephaly cases or 10.4% of all congenital infections). Conclusion: In Rio Grande do Sul, where no outbreak of ZIKV infection was recorded, congenital infections were the leading cause of congenital microcephaly, and the attributable risk for CZS in the etiology of microcephaly was 5.2%.

Resumo: Objetivo: Identificar as causas da microcefalia congênita no Rio Grande do Sul, Região Sul do Brasil, onde não foi detectado surto de ZIKV, de dezembro de 2015 a dezembro de 2016. Esse foi o período em que a infecção por ZIKV estava em seu auge no Nordeste do Brasil. Métodos: Este é um estudo transversal no qual todas as notificações de microcefalia congênita no estado do Rio Grande do Sul foram incluídas para análise. A avaliação dos casos seguiu as orientações do Ministério da Saúde. A avaliação dismorfológica e neurológica foi feita por uma equipe especializada e os testes genéticos e as neuroimagens foram feitos quando indicado clinicamente. As infecções STORCH (Sífilis, Toxoplasmose, Rubéola, Citomegalovírus e Herpes simples) foram diagnosticadas utilizando testes padrão. A infecção por ZIKV foi diagnosticada por meio da transcriptase reversa seguida de reação em cadeia da polimerase (RT-PCR) no soro materno e/ou neuroimagem associada a critérios clínicos/epidemiológicos. Resultados: De 153.744 nascidos vivos registrados no período do estudo, 148 bebês foram casos notificados, porém 90 (60,8%) casos foram excluídos posteriormente como microcefalia "não confirmada". Nos 58 casos confirmados de microcefalia (prevalência = 3,8/10.000 nascidos vivos), as infecções congênitas (sífilis, toxoplasmose, citomegalovírus e ZIKV) constituíram a etiologia predominante (50,0%), seguidas de doenças ligadas ao SNC isolado (15,5%) e síndromes genéticas (10,3%). A síndrome congênita do ZIKV (SCZ) com fenótipo típico foi diagnosticada em três casos (5,2% de todos os casos confirmados de microcefalia ou 10,4% de todas as infecções congênitas). Conclusão: No Rio Grande do Sul, Brasil, onde não foi registrado surto de infecção por ZIKV, a principal causa de microcefalia congênita foram infecções congênitas e o risco atribuível para SCZ na etiologia de microcefalia foi de 5,2%.

Prevalence and causes of congenital microcephaly in the absence of a Zika virus outbreak in southern Brazil.

OBJECTIVE: The aim of this study was to identify the causes of congenital microcephaly in Rio Grande do Sul, a state in southern Brazil, where no ZIKV outbreak was detected, from December 2015 to December 2016, which was the period when ZIKV infection was at its peak in northeast Brazil. METHODS: This was a cross-sectional study where all notifications of congenital microcephaly in the state of Rio Grande do Sul were included for analysis. Evaluation of cases followed the guidelines of the Brazilian Ministry of Health. Dysmorphological and neurological evaluations were performed by a specialized team, and genetic tests and neuroimaging were performed when clinically indicated. STORCH infections were diagnosed using standard tests. ZIKV infection was diagnosed through maternal serum RT-PCR and/or neuroimaging associated with clinical/epidemiological criteria. RESULTS: From 153744 registered live births in the study period, 148 cases were notified, but 90 (60.8%) of those were later excluded as "non-confirmed" microcephaly. In the 58 confirmed cases of microcephaly (prevalence = 3.8/10000 live births), congenital infections (syphilis, toxoplasmosis, cytomegalovirus, and ZIKV) constituted the predominant etiology (50.0%), followed by isolated CNS (15.5%), and genetic syndromes (10.3%). Congenital ZIKV syndrome (CZS) with typical phenotype was diagnosed in three cases (5.2% of all confirmed microcephaly cases or 10.4% of all congenital infections). CONCLUSION: In Rio Grande do Sul, where no outbreak of ZIKV infection was recorded, congenital infections were the leading cause of congenital microcephaly, and the attributable risk for CZS in the etiology of microcephaly was 5.2%.

Idade materna e condições perinatais, entre nascimentos de risco de 2008 a 2013 / Maternal age and perinatal conditions between births at risk from 2008 to 2013 / Edad materna y condiciones perinatales, entre nacimientos de riesgo de 2008 a 2013

Objetivo: investigar el perfil de los recién nacidos y de las puérperas (Mujer que hace muy poco que ha parido) con edad hasta 19 años y superior a 35 años, catastradas en el "Programa Prá-Nenê". Metodología: estudio transversal, observacional, descriptivo, retrospectivo, con abordaje cuantitativo. Los datos fueron obtenidos a través del banco de datos del "Programa de Vigilância de Recém-nascido de risco Prá-nenê", en el período de 2008 a 2013, en municipio de Pelotas-RS. Se utilizó el software Stata 12.0 para el análisis descriptivo de las variables. El presente estudio fue aprobado por el comité de ética en investigación sob nº13348013.8.0000.5317. Resultados: la muestra fue de 1306 puérperas, de estas 706 eran adolescentes y 600 tenían 35 años o más. Se evidenció que las adolescentes realizaron menor número de consultas de prenatal (43,8%) e iniciaron más tardíamente el seguimiento cuando comparadas con mujeres maduras. La frecuencia de partos vaginales disminuye con el aumento de la edad (38,2%). Los recién nacidos de puérperas adolescentes tuvieron un mayor bajo peso al nacer (43,9%), mientras que las madres tuvieron hijos con mayor peso al nacer (37,6%). Conclusión: se reafirma así la necesidad de mayores inversiones en la prevención y promoción de la salud materna, principalmente en los extremos de edad.

Objetivo: investigar o perfil dos recém-nascidos e das puérperas com idade até 19 anos e superior a 35 anos, cadastradas no "Programa Prá-Nenê". Metodologia: estudo transversal, observacional, descritivo, retrospectivo, com abordagem quantitativa. Os dados foram obtidos através do banco de dados do "Programa de Vigilância de Recém-nascido de risco Prá-nenê", período de 2008 a 2013, no município de Pelotas-RS. Foi utilizado o Software Stata 12.0 para análise descritiva das variáveis. O presente estudo foi aprovado pelo comitê de ética em pesquisa sob nº 13348013.8.0000.5317. Resultados: a amostra foi de 1306 puérperas, destas 706 eram adolescentes e 600 tinham 35 anos ou mais. Evidenciou-se que as adolescentes realizaram menor número de consultas de pré-natal (43,8%) e iniciaram mais tardiamente o acompanhamento quando comparadas com mulheres maduras. A frequência de partos vaginais diminui com o aumento da idade (38,2%). Os recém-nascidos de puérperas adolescentes tiveram um maior baixo peso ao nascer (43,9%), enquanto as mães maduras tiveram filhos com maior peso ao nascer (37,6%). Conclusão: reafirma-se assim a necessidade de maiores investimentos na prevenção e promoção da saúde materna, principalmente nos extremos etários.

Objective: investigating the profile of the newborns and the puerperal women aged until 19 years old and older than 35 years old registered at "Programa Prá-Nenê". Methodology: a cross-sectional observational study, with descriptive, retrospective and quantitative approach. Software Stata 12.0 was used for descriptive analysis of the variables. Data were obtained from the "Programa de Vigilância de Recém-Nascido Prá-Nenê" database, from 2008 to 2013, in Pelotas-RS. This study was approved by the local research ethics committee by nº 13348013.8.0000.5317. Results: the sample contained 1306 puerperal women, of which 706 were adolescents and 600 were 35 years old or more. It was evidenced that adolescents had a smaller amount of prenatal visits (43,8%) and had their first prenatal visit later in gestation when compared to mature women. The frequency of vaginal delivery gets smaller with the increase in age (38,2%). The newborns from puerperal teenagers had a smaller birth weight (43,9%), while mature women had newborns with a bigger birth weight. Conclusions: the necessity of more investments in health prevention and promotion is reassured, mainly in early and mature reproductive ages

Epidemiological profile of 39 cases of microcephaly caused by congenital infections diagnosed in the state of Rio Grande do Sul between 2015-2017

Introduction: Microcephaly is a clinical finding that can arise from congenital anomalies or emerge after childbirth. Maternal infections acquired during pregnancy can result in characteristic brain damage in the newborn (NB), which may be visible even in the fetal stage. To describe the epidemiological profile of newborns with reported microcephaly and diagnosed with congenital infections in the state of Rio Grande do Sul between 2015 and 2017. Methods: A cross-sectional study was carried out on data collected from the Public Health Event Registry as well as from medical records. The investigation included serologies for toxoplasmosis and rubella; polymerase chain reaction (PCR) for Zika virus (ZIKV) in the blood and cytomegalovirus in the urine; non-treponemal tests for syphilis; and brain imaging tests. Results: Of the 257 reported cases of microcephaly, 39 were diagnosed with congenital infections. Severe microcephaly was identified in 13 patients (33.3%) and 51.3% of the cases showed alterations in brain imaging tests. In relation to the diagnosis of congenital infections, three patients (7.7%) were diagnosed with ZIKV, nine (23.1%) with cytomegalovirus, nine (23.1%) with toxoplasmosis, and 18 (46.1%) with congenital syphilis. The three cases of ZIKV showed calcification in brain imaging tests, signs of arthrogryposis, excess occipital skin and irritability, characterizing the typical phenotype of ZIKV infection. Conclusions: Most cases of congenital infection had severe neurological lesions, particularly the cases of ZIKV, which can cause neurodevelopmental delays and sequelae in these infants throughout early childhood.

Maple syrup urine disease in Brazil: a panorama of the last two decades / Doença da urina de xarope de bordo no Brasil: um panorama das últimas duas décadas

OBJECTIVE: To characterize a sample of Brazilian patients with maple syrup urine disease (MSUD) diagnosed between 1992 and 2011. METHODS: In this retrospective study, patients were identified through a national reference laboratory for the diagnosis of MSUD and through contact with other medical genetics services across Brazil. Data were collected by means of a chart review. RESULTS: Eighty-three patients from 75 families were enrolled in the study (median age, 3 years; interquartile range [IQR], 0.57-7). Median age at onset of symptoms was 10 days (IQR 5-30), whereas median age at diagnosis was 60 days (IQR 29-240, p = 0.001). Only three (3.6%) patients were diagnosed before the onset of clinical manifestations. A comparison between patients with (n = 12) and without (n = 71) an early diagnosis shows that early diagnosis is associated with the presence of positive family history and decreased prevalence of clinical manifestations at the time of diagnosis, but not with a better outcome. Overall, 98.8% of patients have some psychomotor or neurodevelopmental delay. CONCLUSION: In Brazil, patients with MSUD are usually diagnosed late and exhibit neurological involvement and poor survival even with early diagnosis. We suggest that specific public policies for diagnosis and treatment of MSUD should be developed and implemented in the country. .

OBJETIVO: Caracterizar uma amostra de pacientes brasileiros com a doença da urina de xarope de bordo (DXB) diagnosticados entre 1992 e 2011. MÉTODOS: Os pacientes foram identificados por meio de um laboratório de referência nacional para o diagnóstico de DXB e por meio do contato com outros serviços de genética médica no Brasil. Os dados foram coletados por meio de uma revisão de prontuários. RESULTADOS: Foram incluídos no estudo 83 pacientes de 75 famílias (idade média: três anos; intervalo interquartil (IQR): 0,57-7). A idade média no surgimento dos sintomas era de 10 dias (IQR: 5-30), ao passo que a idade média no diagnóstico era de 60 dias (IQR: 29-240; p = 0,001). Somente três (3,6%) pacientes foram diagnosticados antes do surgimento de manifestações clínicas. Uma comparação entre pacientes com (n = 12) e sem (n = 71) um diagnóstico precoce mostra que o diagnóstico precoce está associado à presença de histórico familiar positivo e à redução na prevalência de manifestações clínicas no momento do diagnóstico, porém sem melhor resultado. Em geral, 98,8% dos pacientes têm algum atraso no desenvolvimento psicomotor ou neurológico. CONCLUSÃO: No Brasil, os pacientes com DXB normalmente recebem um diagnóstico tardio e exibem um envolvimento neurológico e baixa sobrevivência, mesmo com um diagnóstico precoce. Sugerimos que políticas públicas específicas para o diagnóstico e tratamento da DXB sejam desenvolvidas e implementadas no país. .

Maple syrup urine disease in Brazil: a panorama of the last two decades.

OBJECTIVE: To characterize a sample of Brazilian patients with maple syrup urine disease (MSUD) diagnosed between 1992 and 2011. METHODS: In this retrospective study, patients were identified through a national reference laboratory for the diagnosis of MSUD and through contact with other medical genetics services across Brazil. Data were collected by means of a chart review. RESULTS: Eighty-three patients from 75 families were enrolled in the study (median age, 3 years; interquartile range [IQR], 0.57-7). Median age at onset of symptoms was 10 days (IQR 5-30), whereas median age at diagnosis was 60 days (IQR 29-240, p=0.001). Only three (3.6%) patients were diagnosed before the onset of clinical manifestations. A comparison between patients with (n=12) and without (n=71) an early diagnosis shows that early diagnosis is associated with the presence of positive family history and decreased prevalence of clinical manifestations at the time of diagnosis, but not with a better outcome. Overall, 98.8% of patients have some psychomotor or neurodevelopmental delay. CONCLUSION: In Brazil, patients with MSUD are usually diagnosed late and exhibit neurological involvement and poor survival even with early diagnosis. We suggest that specific public policies for diagnosis and treatment of MSUD should be developed and implemented in the country.

Therapy for mucopolysaccharidosis VI: (Maroteaux-Lamy syndrome) present status and prospects.

Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disorder caused by deficient activity of Arylsulphatase B (ARSB). The disease is progressive and multisystemic, usually leading to death in the first decades of life. In addition to supportive management, specific treatments for MPS VI are the hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT). Both are effective for some aspects of the disease, but fail in correcting important clinical features, such as bone deformities and heart valve thickening. Based on that, new treatments are currently being tested to be used alone or in combination with the current therapies. Here we summarize some of these new approaches and the preliminary results obtained, reporting their limitations and indicating possible future trends in MPS VI treatment. We discuss intrathecal ERT, gene therapy and therapies based on anti-inflammatory molecules, among other approaches. Finally, we highlight the importance of early treatment and diagnosis for a better outcome in these patients.

Recent Advances in Treatment Approaches of Mucopolysaccharidosis VI.

Mucopolysaccharidosis VI is caused by accumulation of the glycosaminoglycan dermatan sulfate in all tissues due to decreased activity of the enzyme arylsulfatase B. Patients exhibit multisystemic signs and symptoms in a chronic and progressive manner, especially with changes in the skeleton, cardiopulmonary system, cornea, skin, liver, spleen and meninges. Patients usually have normal intelligence. In the past, treatment of mucopolysaccharidoses was limited to palliative medical care. The outcome for affected patients improved with the introduction of new technologies as hematopoietic stem cell transplantation, relegated to specific situations after enzyme replacement therapy (ERT) became available. The specific ERT for MPS VI, galsulfase (Naglazyme®, Biomarin Pharmaceutical) was approved in 2005 by FDA and in 2006 by EMEA, and three clinical studies including 56 patients have evaluated the efficacy and safety. Long-term follow up data with patients treated up to 5 years showed that ERT is well tolerated and associated with sustained improvements in the patients' clinical condition. Intrathecal ERT may be considered in situations of high neurosurgical risk but still it is experimental in humans, as is intra-articular ERT. It is possible that the full impact of this therapy will only be demonstrated when patients are identified and treated soon after birth, as it was shown that early introduction of ERT produced immune tolerance and improved enzyme effectiveness in the cat model. New insights on the pathophysiology of MPS disorders are leading to alternative therapeutic approaches, as gene therapy, inflammatory response modulators and substrate reduction therapy.

DNA damage in leukocytes from pretreatment mucopolysaccharidosis type II patients; protective effect of enzyme replacement therapy.

Mucopolysaccharidosis type II (MPS II) is an X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase, leading to progressive accumulation of glycosaminoglycans in nearly all cell types, tissues and organs. Enzyme replacement therapy reduces the storage of these substances in the lysosomes. Oxidative stress is related to the pathophysiology of many disorders, including inborn errors of metabolism. Oxidative damage to protein and lipid has been described in MPS types I and III. The aim of this study was to analyze DNA damage, as determined by the alkaline comet assay using silver staining, in peripheral leukocytes from MPS II patients before treatment and during the first six months of enzyme replacement therapy. We also correlated DNA damage with lipid and protein oxidative damages, analyzed by plasma malondialdehyde levels and carbonyl group content, respectively. We found a significant increase in lipid and protein damage in MPS II patients before treatment when compared to controls. Also, our results showed greater DNA damage in terms of damage index (DI) in pretreatment MPS II patients (DI=18.0 ± 2.4) when compared to controls (DI=66.0 ± 2.0). Enzyme replacement therapy led to a significant decrease in levels of malondialdehyde and DNA damage when compared to pretreatment, but did not reach control values. Significant positive correlations between DNA damage and malondialdehyde levels, as well as carbonyl group content, were observed. Our findings indicate that MPS II patients are subject to DNA damage and that enzyme replacement therapy is able to protect against this process.