RESUMO Paciente portadora de deficiência de acil-CoA desidrogenase de cadeia média (MCADD), com episódios clínicos recorrentes de hipoglicemia e alteração de consciência, apresentou alterações no perfil de acilcarnitinas em sangue por espectrometria de massas em tandem e na análise de ácidos orgânicos urinários por cromatografia gasosa acoplada à espectrometria de massa. Este caso demonstra a importância da coleta de amostra biológica em jejum (se possível) quando há suspeita de MCADD e ressalta que o tempo/momento de coleta da amostra biológica é importante para o diagnóstico, considerando a possibilidade de a MCADD ser subdiagnosticada no Brasil.

ABSTRACT Female patient carrier of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) with recurrent clinical episodes of hypoglycemia and altered level of consciousness, presented changes in blood acylcarnitine profile by tandem mass spectrometry and in the urinary organic acid analysis by gas chromatography/mass spectrometry (GC/MS). This case demonstrates the importance of fasting prior biological sample collection (when possible) when MCADD is suspected, and emphasizes that the time/momentum of biological sample collection is crucial to diagnosis, considering the possibility that MCADD is underdiagnosed in Brazil.

RESUMEN Paciente portadora de deficiencia de acil-CoA deshidrogenasa de cadena media (MCADD) con episodios clínicos recurrentes de hipoglucemia y alteración de consciencia presentó mudanzas en el perfil de acilcarnitinas en la sangre con técnicas de espectrometría de masas en tándem y en el análisis de ácidos orgánicos urinarios mediante cromatografía de gases acoplada a espectrometría de masas. Este caso demuestra la importancia de la toma de muestras biológicas en ayunas (se posible) cuando se sospecha de MCADD y destaca que el tiempo/momento de extracción de la muestra biológica es valioso para el diagnóstico, considerando la posibilidad de que la MCADD es subdiagnosticada en Brasil.

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%.

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%.

Abstract Introduction: Newborn Screening Program (NBS) in Uruguay includes congenital hypothyroidism (CHT), phenylketonuria (PKU), congenital adrenal hyperplasia (CAH), cystic fibrosis (CF), medium chain acyl-CoA dehydrogenase deficiency (MCADD), and Congenital Hearing Loss (CHL). Objetives: This study describe the epidemiological characteristics of newborns with abnormal neonatal screening tests diagnosed by blood drop and otoacoustic emissions in Uruguay. Results: Cases with abnormal NBS tests (399 newborns; 0.17%) were compared to the newborns with normal tests in the same period (239,240). Prevalence rates (per 10,000 livebirths) were 10.00 for CHL; 3.70 for CH; 1.20 for CF; 0.59 for CAH; 0.54 for PKU; 0.13 for MCADD. The Department of Artigas had the highest rate of abnormal tests. Lower maternal education, less prenatal care, increased prematurity rate and neonatal depression were more frequent in in mothers whose children had CHL. Conclusions: This is the first study evaluating the characteristics of newborns with abnormal screening in Uruguay. Because these results may impact the planning of health services, data transmission between clinical care and public health systems is needed to improve both follow-up and management.

Campomelic dysplasia (CD) is an autosomal, dominantly inherited, skeletal abnormality belonging to the subgroup of bent bone dysplasias. In addition to bowed lower limbs, CD typically includes the following: disproportionate short stature, flat face, micrognathia, cleft palate, bell-shaped thorax, and club feet. Up to three quarters of 46, XY individuals may be sex-reversed. Radiological signs include scapular and pubic hypoplasia, narrow iliac wings, spaced ischia, and bowed femora and tibiae. Lethal CD is usually due to heterozygous mutations in SOX9, a major regulator of chondrocytic development. We present a detailed clinical and molecular characterization of nine Brazilian CD patients. Infants were either stillborn (n = 2) or died shortly after birth and presented similar phenotypes. Sex-reversal was observed in one of three chromosomally male patients. Sequencing of SOX9 revealed new heterozygous mutations in seven individuals. Six patients had mutations that resulted in premature transcriptional termination, while one infant had a single-nucleotide substitution at the conserved splice-site acceptor of intron 1. No clear genotype-phenotype correlations were observed. This study highlights the diversity of SOX9 mutations leading to lethal CD, and expands the group of known genetic alterations associated with this skeletal dysplasia.

The study of the fetal karyotype became an important tool for the fetal diagnosis of genetic diseases in the 1970s. Although application of this test has remained very restricted in Brazil, we had 905 referrals for prenatal fetal karyotyping between 1989 and 2007. In 879 cases, a fetal karyotype was obtained. We detected 74 abnormal karyotypes (8.4%), the majority being found when the prior indication was fetal malformation. When obtaining amniotic fluid or chorionic villus samples was difficult, alternative fetal materials (urine, cystic hygroma, cystic lung, intreperitoneal and cerebrospinal fluids) were collected and we had success in obtaining karyotypes in all 13 cases. Although, the option of terminating abnormal pregnancies does not legally exist in Brazil, the information gained in assessing the prognosis of on-going pregnancies or estimating recurrence risks justifies prenatal diagnosis of chromosome abnormalities. We conclude that, in keeping with the policy in most other countries, prenatal cytogenetic analysis is strongly recommended in high-risk pregnancies for fetal abnormalities. However, the unique aspect of this type of study is not its rarity in world terms, but its rarity in Brazil. This argues that Brazilian health policy on prenatal diagnosis requires reforming to make it much more widely available within the public health care sector.

OBJETIVO: Ainda que as características clássicas da síndrome fetal alcoólica tenham sido descritas desde 1968, a pesquisa sobre a teratogênese do álcool apenas recentemente demonstrou que o cérebro é o órgão do corpo mais vulnerável aos efeitos da exposição pré-natal ao álcool. No presente artigo, fazemos uma revisão da literatura focalizando principalmente os distúrbios comportamentais relacionados à exposição pré-natal ao álcool. FONTES DOS DADOS: Foi realizada uma pesquisa com base no PubMed sobre a literatura publicada entre 1968 e 2006, com as palavras-chave etanol, gestação e comportamento. Foram estabelecidos limites a estudos em humanos. SÍNTESE DOS DADOS: Os dados apresentados nesta revisão sugerem que jovens com efeitos do espectro do álcool fetal estão sob risco maior de terem comportamento social disruptivo, entre outros problemas neurocomportamentais. CONCLUSÕES: Ainda que seja impossível separar completamente a teratogênese sobre o cérebro decorrente da exposição ao álcool de influências ambientais pós-natais como a causa definitiva desses resultados, o pediatra deve ser estimulado ao diagnóstico precoce de crianças afetadas pela síndrome fetal alcoólica e efeitos do espectro do álcool fetal. Isso permite iniciar o manejo e cuidados apropriados para evitar as conseqüências em longo prazo no comportamento e assegurar uma adaptação social e escolar melhor e mais produtiva.

OBJECTIVE: Although the classic features of fetal alcohol syndrome have been recognized since 1968, research on alcohol teratogenesis has only recently demonstrated that the brain is the organ in the body most vulnerable to the effects of prenatal alcohol exposure. In this present article, we reviewed the literature focusing mainly on behavioral disturbances related to prenatal ethanol exposure. SOURCES: We performed a PubMed search on the literature published between 1968 and 2006 using the terms ethanol, pregnancy and behavior. We limited our search to studies on humans. SUMMARY OF THE FINDINGS: The data presented in this review suggested that youths with fetal alcohol spectrum disorder are at risk of disruptive social behavior, among other neurobehavioral abnormalities. CONCLUSIONS: Although it is still impossible to completely separate brain teratogenesis secondary to alcohol exposure from environmental postnatal influences as the definite cause for these outcomes, the pediatrician should be encouraged to early diagnose children affected by fetal alcohol syndrome and fetal alcohol spectrum disorder. This provides proper management and care and avoids long-term consequences on their behavior, besides ensuring better and productive school and social adaptation.