The diagnosis of von Willebrand disease (VWD), the most common inherited bleeding disorder, is characterised by a variable bleeding tendency and heterogeneous laboratory phenotype. The sequencing of the entire VWF coding region has not yet become a routine practice in diagnostic laboratories owing to its high costs. Nevertheless, next-generation sequencing (NGS) has emerged as an alternative to overcome this limitation. We aimed to determine the correlation of genotype and phenotype in 92 Portuguese individuals from 60 unrelated families with VWD; therefore, we directly sequenced VWF. We compared the classical Sanger sequencing approach and NGS to assess the value-added effect on the analysis of the mutation distribution in different types of VWD. Sixty-two different VWF mutations were identified, 27 of which had not been previously described. NGS detected 26 additional mutations, contributing to a broad overview of the mutant alleles present in each VWD type. Twenty-nine probands (48.3 %) had two or more mutations; in addition, mutations with pleiotropic effects were detected, and NGS allowed an appropriate classification for seven of them. Furthermore, the differential diagnosis between VWD 2B and platelet type VWD (n = 1), Bernard-Soulier syndrome and VWD 2B (n = 1), and mild haemophilia A and VWD 2N (n = 2) was possible. NGS provided an efficient laboratory workflow for analysing VWF. These findings in our cohort of Portuguese patients support the proposal that improving VWD diagnosis strategies will enhance clinical and laboratory approaches, allowing to establish the most appropriate treatment for each patient.

INTRODUÇÃO: o baixo peso ao nascer (BPN) é considerado um dos mais importantes problemas de saúde pública em todo o mundo, contribuindo, substancialmente, para a morbi-mortalidade infantil. OBJETIVOS: estimar a proporção de baixo peso ao nascer e identificar os fatores associados. MÉTODO: estudo transversal onde se analisaram 3220 declarações de nascidos vivos referentes aos partos ocorridos no município de Cruzeiro do Sul, Estado do Acre, no período de 2006 e 2007, de mães residentes nesta localidade. Na análise, utilizou-se regressão linear generalizada família Poisson ligação logarítmica com variância robusta, simples e múltipla. Adotou-se nível de significância de 0,10. RESULTADOS: a proporção de baixo peso ao nascer foi 9,13%. Os fatores associados ao baixo peso ao nascer foram: prematuridade; nascimento no domicílio; sexo feminino; idades maternas entre 12 e 13 anos, 16 e 17 anos, 18 e 19 anos, 35 e mais anos; realização de 1 a 3 consultas de pré-natal, crianças não brancas, mães sem ocupação fora do lar e mães solteiras. CONCLUSÃO: são poucos (ou nenhum) os fatores suscetíveis de mudança ou controle com ações isoladas de saúde. Estratégias de ampla abrangência são necessárias para a redução da proporção de baixo peso ao nascer em Cruzeiro do Sul, Acre e, uma vez ocorrido baixo peso ao nascer, atenção especial deve ser proporcionada à criança.

OBJECTIVE:To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS:A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors "childhood leukemia" and "infection" and later searching for the words "childhood leukemia" and "maternal infection or disease" or "breastfeeding" or "daycare attendance" or "vaccination" resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers' or infants' to infections (or proxy of infection), and risk of leukemia. RESULTS:Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori. CONCLUSIONS:Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology. DESCRIPTORS:Children. Leukemia, etiology. Causality. Infection. Review. Leukemia makes up about one third of all malignancies in the 0-14 year old age group. The most common subtype, acute lymphoblastic leukemia (ALL), represents about 80.0% of these cases. 57 The incidence rate of ALL was estimated as 35.2 per million children aged under 15 in Brazil, and children under five are the most affected. 60Potential risk factors for childhood leukemia (CL) are conflicting. Exposure to ionizing radiation, commonly accepted as a cause of leukemia, does not explain all cases of leukemia in children.5 The etiology of CL has a multifactorial character. Leukemic cells that carry genetic alterations arise mainly before birth. Translocation between chromosomes 12 and 21 causes fusion of the TEL and AML1 gene; producing aberrant proteins that inhibit gene activity and change the capacity for self-renewal and differentiation of hematopoietic stem cells; this change represents the most common structural genetic abnormality in children with leukemia.45,74 About 1.0% of healthy newborns have this translocation and one RESUMO OBJETIVO: Analisar estudos que avaliaram o papel de infecções e de medidas indiretas de exposição às infecções no risco de leucemia infantil, principalmente da leucemia linfocítica aguda. MÉTODOS:A busca nas bases de dados Medline, Lilacs e SciELO utilizando-se inicialmente os de...

OBJECTIVETo analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia.METHODSA search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors "childhood leukemia" and "infection" and later searching for the words "childhood leukemia" and "maternal infection or disease" or "breastfeeding" or "daycare attendance" or "vaccination" resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers' or infants' to infections (or proxy of infection), and risk of leukemia.RESULTSOverall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori.CONCLUSIONSAlthough no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology.

Acute secondary neurological deterioration after herpes simplex encephalitis has been reported. An immune-mediated process is thought to be responsible for some cases. The authors report the case of an infant who presented with fever, irritability, and orofacial involuntary movements, 15 days after herpes encephalitis onset. Polymerase chain reaction for herpes simplex virus was negative, and the magnetic resonance imaging revealed extensive white matter lesions. Chorea appeared only 11 days later. Raised immunoglobulin G index with oligoclonal bands and spreading of white matter lesions corroborated an immune-mediated etiology. An interferon production deficit was also detected. This case alerts that this form of ''relapse'' appears earlier than previously reported. A high level of suspicion is needed in the presence of atypical neurological deterioration and early white matter lesions should be considered as a warning sign. This case is also relevant because it associates, for the first time, an immune-mediated ''relapse'' to an interferon production deficit.