Information and Diagnosis Networks - tools to improve diagnosis and treatment for patients with rare genetic diseases.

Brazil is a country of continental dimensions and most genetic services are concentrated in the Southeast and South, including the Medical Genetics Service of the Hospital de Clínicas de Porto Alegre (MGS/HCPA). As many areas on the country do not have adequate medical genetics support, networks were designed to extend the service of the MGS/HCPA reference center. This paper presents the information and diagnosis networks that have their headquarters at MGS/HCPA: SIAT (National Information System on Teratogenic Agents), SIEM (Information Service on Inborn Errors of Metabolism), Alô Genética (Hello Genetics - Medical Genetics Information Service for Primary Health Care Professionals); Rede MPS Brasil (MPS-Mucopolysaccharidosis Brazil Network); Rede EIM Brasil (IEM-Inborn Errors of Metabolism Brazil Network), Rede NPC Brasil (Niemann-Pick C - NPC Brazil Network), Rede DLD Brasil (LSD-Lysosomal Storage Disorders Brazil Network), Rede DXB (MSUD-Maple Syrup Urine Disease Network), RedeBRIM (Brazilian Network of Reference and Information in Microdeletion Syndromes Project), Rede Neurogenética (Neurogenetics Network), and Rede Brasileira de Câncer Hereditário (Brazilian Hereditary Cancer Network). These tools are very useful to provide access to a qualified information and/or diagnostic service for specialized and non-specialized health services, bypassing difficulties that preclude patients to access reference centers.

Biochemical composition of the saliva and dental biofilm of children with Down syndrome.

BACKGROUND: The biochemical composition of the saliva and biofilm of children with Down syndrome (DS) may be associated with the incidence of caries in this population. AIM: To evaluate the biochemical composition of the saliva and dental biofilm of children with DS in the city of Porto Alegre, RS. DESIGN: The sample comprised 144 children between 6 and 14 years of age, of whom 61 had DS and 83 did not. Stimulated saliva samples were collected from all participants, as were samples of 48-h biofilm. Fluoride (F), calcium (Ca), and phosphorus (Pi ) concentrations in saliva and biofilm were determined by colorimetric method (Ca and Pi ) or selective electrode (F). The level of insoluble extracellular polysaccharide (EPS) in dental biofilm was measured using sulphuric acid method. RESULTS: Salivary concentration of F, Ca, and Pi did not differ between children with and without DS. The dental biofilm of children with DS, however, showed higher Pi and EPS levels than that of children without the syndrome (P < 0.05). CONCLUSIONS: The present results suggest that despite the salivary composition being similar between groups, the dental biofilm of children with DS has higher cariogenic potential than that of children without this condition.

Neurological evaluation of microcephalic children with Zika syndrome and congenital cytomegalovirus infection.

Introduction: The association between the virus prenatal infection by Zika virus (ZIKV) and central nervous system disorders has been well established and it has been described as the Congenital Syndrome Associated to the Zika Virus (CSZ). However, the neurological development in those patients is still an object of study. The main differential diagnosis is the Cytomegalovirus (CMV). Objective: Describe the involvement of microcephalic patients affected by the congenital infection by the Zika Virus or CMV. Methodology: Data has been collected from microcephalic patients whose birth took place after 2016 and which also had the congenital infection confirmed or presumed. The researched data consists in: congenital infection, head circumference from birth, presence of epilepsy, treatment by mono or polytherapy, electroencephalographic patterns, neurological physical examination and evaluation of gross motor development. Results: 21 microcephalic children have been included showing the following congenital infectious syndromes: 9 were affected by cytomegalovirus (43%), 6 by the Zika virus (29%) and 6 ones by presumed infection due to the Zika virus (29%). From those ones, 13 (62%) presented epilepsy diagnosis including generalized crises and 9 (69%) were in current use of polytherapy. All of them also showed disorganized and asymmetrical base rhythms. Concerning the epileptiform activity, 5 presented multifocal activity and 3 ones hypsarrhythmia. All of the patients went under neuroimaging: 12 (57%) of them presented calcifications and 5 (24%) hydrocephalus. On the neurological exam, 17% presented a decreased axial tone and an enlarged appendicular. Smaller head circumference children had greater motor impairment and severity in the epilepsy. There was no difference in the frequency of epilepsy between children with CSZ and CMV. Conclusion: Epilepsy is confirmed as one of the most important complications of congenital infections by CSZ and CMV.

Genotypic diversity and acidogenicity of Streptococcus mutans in Down syndrome children.

AIMS: To evaluate the genotypic diversity and acidogenicity of Streptococcus mutans (S. mutans) and the potential association of these factors with dental caries experience in children with DS compared to non-DS children (controls). METHODS AND RESULTS: Seventeen children (age 6-12 years) with high salivary S. mutans counts (> 2.5 × 105 CFU/mL) were selected and divided into two groups: DS and non-DS. Five children in each group were caries-free, while the remainder had elevated caries experience. S. mutans isolates were obtained from each participant. The genotypic profile of the isolates was analyzed with the AP-PCR methodology. The acidogenicity of a representative strain from each genotype of S. mutans was also evaluated. DS children had 16 different S. mutans genotypes, while the control group had 21. Twelve genotypes were present in both groups and one of them was associated with caries-free status (P < .05). Although the acidogenicity of the genotypes found in DS children was significantly lower (P < .05) compared to controls, this fact was not associated with caries experience in both groups. CONCLUSIONS: DS children have a lower S. mutans genotypic diversity and genotypes with lower acidogenicity than those of non-DS children. However these findings were not associated with their caries experience.

Salivary secretory IgA concentration and dental caries in children with Down syndrome.

PURPOSE: To evaluate the relationship between salivary secretory immunoglobulin A (sIgA) concentration and dental caries in children with Down syndrome (DS) and compare it with findings in non-DS children. METHODS: The sample comprised 61 DS children and 52 non-DS children, aged 6 to 14 years. Caries experience, plaque index (PI), and gingival bleeding index (GBI) were recorded. Saliva samples were collected from all children. Total salivary sIgA concentrations were determined using an enzymatic assay method. RESULTS: Caries experience in primary and permanent dentitions were similar in DS and non-DS children. However, PI and GBI values were significantly lower in DS compared to non-DS children. DS children had higher salivary sIgA concentrations compared to non-DS children. No difference in sIgA concentration was observed between children with and without caries experience in either group. CONCLUSIONS: DS children have higher salivary sIgA concentrations than non-DS children. However, this finding did not correlate with caries experience in the study population.

Oral Health Status and Salivary Levels of Mutans Streptococci in Children with Down Syndrome.

PURPOSE: The literature on the oral health status of Down syndrome (DS) patients is controversial. Therefore, the purpose of this study was to assess the oral health status and levels of mutans streptococci (MS) in the saliva of DS children. METHODS: This study was performed with 60 DS children and 71 non-DS children aged six to 12 years old. Caries experience, plaque index (PI), and gingival bleeding index (GBI) were recorded. Information about oral hygiene habits was obtained. Saliva samples were collected to determine MS levels. RESULTS: The prevalence of dental caries was similar in children with and without DS. DS children had lower PI and GBI values and a higher toothbrushing frequency. Supervised toothbrushing by parents or guardians was more frequent in DS children and associated with lower PI and GBI. High counts of MS in saliva were associated with caries experience in DS children. CONCLUSIONS: Down syndrome children had a similar caries experience, lower plaque index, and lower gingival bleeding index values compared to children without Down syndrome. However, DS children who had caries were more likely to display high counts of mutans streptococci in saliva than non-DS children with caries.

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.

Microcefalia e Zika Vírus: características e associações / Microcephaly and Zika Virus: clinical features and associations / Microcefalia y Virus Zika: características y asociaciones

Objetivo: Discutir a associação entre microcefalia e a infecção materna por Zika Vírus. A microcefalia é o tamanho da cabeça menor do que o esperado em comparação com bebês do mesmo sexo e idade. Entre as causas conhecidas, estão as infecções congênitas. O aumento de casos entre outubro e novembro de 2015 no nordeste brasileiro, que coincidiu com a presença da circulação de novo vírus no país, em maio do mesmo ano, criou a hipótese de associação entre a microcefalia e a infecção materna durante a gravidez. O Zika Vírus é um arbovírus similar ao da Febre Amarela e da Dengue, transmitido principalmente através da picada do Aedes aegypti. A provável transmissão por relação sexual e transfusão de sangue, além de outros vetores como o Aedes albopictus e possivelmente até o pernilongo (Culex sp) aumentam a necessidade de cuidados preventivos em relação à infecção. O exame para detecção viral idealmente é realizado até o quinto dia após o início dos sintomas. Sorologias ainda não são amplamente disponíveis no Brasil. Métodos: Revisão narrativa da literatura. Conclusão: A associação entre casos de microcefalia e o Zika Vírus é embasada nos relatos de relação têmporo-espacial, padrão de alterações neurológicas associado a malformações congênitas, presença do RNA viral no líquido amniótico e nos tecidos de fetos. As respostas definitivas de causalidade serão possíveis após pesquisas e disponibilidade de exames laboratoriais. As evidências até agora apoiam fortemente esta hipótese e todas as medidas preventivas devem ser estimuladas.

Objective: To discuss the association between microcephaly and intrauterine infection by Zika virus. Microcephaly occurs when a child is born with a head smaller than expected when compared to babies of the same sex and age. Known causes of microcephaly include congenital infections. The increase in the number of microcephaly cases in Northeast Brazil between October and November 2015, which coincided with the emergence of Zika virus in the country in May of the same year, led to the hypothesis of an association between microcephaly and intrauterine Zika virus infection. Zika is an arbovirus that is closely related to yellow fever and dengue viruses. Aedes aegypti mosquitoes are the primary vector of transmission. Possible transmission through sexual contact and blood transfusion, as well as the implication of other vectors, such as Aedes albopictus and even Culex sp increases the need for preventive action. The test for viral detection is ideally performed before the 5th day following the onset of symptoms. Serology tests are not yet widely available in Brazil. Methods: We performed a narrative literature review. Conclusion: The hypothesis of an association between microcephaly and Zika virus is based on reports of spatial/temporal relationship, pattern of neurologic alterations associated with congenital malformations, and findings of viral RNA in amniotic fluid and fetal tissue. Definitive conclusions about the causality can only be reached after further research and availability of laboratory tests. The current evidence strongly supports the association between microcephaly and Zika infection, and all preventive measures must be stimulated.

Objetivo: Discutir las asociaciones entre microcefalia e infección materna por Virus Zika. La microcefalia es el tamaño de la cabeza menor de lo esperado en comparación con los bebés del mismo sexo y edad. Entre las causas conocidas están las infecciones congénitas. El aumento de casos entre octubre y noviembre de 2015 en el nordeste de Brasil, que coincidió con la presencia de la nueva circulación del virus en el país en mayo del mismo año, creó la hipótesis de asociación entre la microcefalia y la infección de la madre por Virus Zika durante el embarazo. El virus Zika es un arbovirus similar al dengue y la fiebre amarilla. El virus se transmite a través de la picadura del mosquito Aedes aegypti. La probable transmisión por vía sexual y por la transfusión de sangre - además de otros vectores como el Aedes albopictus y posiblemente el mosquito Culex sp - aumentan la necesidad de atención preventiva contra la infección. El cuadro clínico es benigno, autolimitado, caracterizado por erupción maculopapular asociado con otros síntomas tales como conjuntivitis, artralgia y la inflamación de las articulaciones. El examen para la detección del virus se realiza idealmente por el quinto día después de la aparición de los síntomas. Las pruebas serológicas no están ampliamente disponibles en Brasil. Métodos: Revisión de literatura. Conclusión: La asociación entre los casos de microcefalia y el virus Zika se basa en informes de patrón de relación temporo-espacial de los trastornos neurológicos asociados con malformaciones congénitas, el ARN viral presente en el líquido amniótico y tejidos de fetos. Las respuestas definitivas de causalidad serán posibles después de la investigación y la disponibilidad de pruebas de laboratorio. Hasta ahora, las evidencias apoyan firmemente esta hipótesis y todas las medidas preventivas deben ser estimuladas.

O uso de larvicidas em água potável é seguro? / Is the use of larvicides in drinking water safe? / ¿El uso de lavicida en la agua potable es seguro?

Provavelmente sim. Não existem evidências que comprovem a segurança do uso de larvicidas em água potável. Entretanto, os poucos estudos que existem avaliando o efeito em população de mamíferos, assim como as avaliações de biodisponibilidades e citotoxicidade, demonstram que em baixa concentração são seguros e não há efeitos carcinogênicos ou genotóxico. Os larvicidas avaliados e autorizados para uso em água potável pela Organização Mundial de Saúde, destinada para consumo humano são: DIFLUBENZUROM, METOPRENO, NOVALUROM, Pirimifós/, PIRIPROXIFEM, ESPINOSADE, TEMEFÓS, além do Bacillus thuringiensis israelensis (BTI). Recomenda-se sempre usar a dose correta dos larvicidas. O temephós é utilizado para tratamento de focos, mas não deve ser utilizado em aquários com peixes. Aprovado para uso em água de consumo humano. O pyriproxyfen é um éter e não há evidências que comprovem que cause dano em fetos de mamíferos. BTI é recomendado como larvicida para uso em saúde pública, é uma bactéria que em contato com a água libera substâncias tóxicas para as larvas de alguns insetos. A aplicação deverá ser realizada por profissional treinado. O BTI não apresenta ingesta diária aceitável, entretanto a orientação de uso deve ser de 1-5mg/litro. A avaliação de substâncias químicas de qualquer natureza sempre deve salientar a possibilidade de bioacumulação. As substâncias que não são biodegradadas, são biopersistentes e mantêm-se em altas quantidades nos tecidos dos seres vivos. Portanto, mesmo que as substâncias não sejam para consumo humano direto a avaliação do seu uso na agricultura, leito de rio e pastos deve ser avaliada criteriosamente.

Probably yes. There is no evidence to prove the safety of the use of larvicides in drinking water. However, there are few studies evaluating the effect on the population of mammals, as are the bioavailabilities and cytotoxicity reviews show that in low concentrations are safe and no genotoxic or carcinogenic effects. Larvicides evaluated and authorized for use in drinking water by the World Health Organization, intended for human consumption are: DIFLUBENZUROM, METOPRENO, NOVALUROM, Pirimifós/, PIRIPROXIFEM, ESPINOSADE, TEMEFÓS, beyond Bacillus thuringiensis israelensis (BTI). It is recommended to always use the correct dose of larvicides. Temephos is used to treat outbreaks, but should not be used in fish tanks. Approved for use in drinking water. The pyriproxyfen is an ether and there is no evidence to support that it causes damage in mammalian fetuses. BTI are recommended as larvicides for use in public health, it is a bacterium that contact with water releases toxic to the larvae of some insects. The application should be performed by trained professional. BTI has no acceptable daily intake, however the guidance of use should be 1-5mg/liter. The evaluation of chemicals of any kind should always stress the possibility of bioaccumulation. Substances that are not biodegraded are biopersistent and remain at high levels in the tissues of living things. So even if the substances are not for direct human consumption, an appraisal of its use in agriculture, river bed and pastures should be carefully evaluated.

Probablemente sí. No hay evidencia para demostrar la seguridad del uso de larvicidas en la agua potable. Sin embargo, hay pocos estudios que evalúan el efecto sobre la población de mamíferos, como son los biodisponibilidad y las revisiones de citotoxicidad muestran que en concentraciones bajas son seguros y sin efectos genotóxicos o cancerígenos. Larvicidas evaluadas y autorizadas para su uso en la agua potable por la Organización Mundial de Salud, destinados al consumo humano son: DIFLUBENZUROM, METOPRENO, NOVALUROM, Pirimifós/, PIRIPROXIFEM, ESPINOSADE, TEMEFÓS, más allá de Bacillus thuringiensis israelensis (BTI). Se recomienda utilizar siempre la dosis correcta de larvicidas. Temephos se utiliza para tratar los brotes, pero no se debe utilizar en los tanques de peces. Aprobado para uso en la agua potable. El piriproxifeno es un éter y no hay evidencia para apoyar que causa daños en los fetos de mamíferos. Se recomienda BTI como larvicida para uso en la salud pública, es una bacteria que en contacto con el agua tóxicas para las larvas de algunos insectos. La aplicación debe ser realizada por profesionales capacitados. BTI no tiene ninguna ingesta diaria admisible, sin embargo, la orientación de uso debe ser 1-5 mg/litro. La evaluación de los productos químicos de cualquier tipo siempre se debe hacer hincapié en la posibilidad de bioacumulación. Las sustancias que no se biodegradan, son biopersistente y se mantienen en niveles altos en los tejidos de los seres vivos. Así que incluso si las sustancias no son para el consumo humano directo, una apreciación de su uso en la agricultura, lecho del río y pastos debe ser cuidadosamente evaluada.