RESUMEN
BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by the deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: BCKDHA, BCKDHB, DBT, and DLD. MSUD is predominantly caused by mutations in the BCKDHA, BCKDHB, and DBT genes which encode the E1α, E1ß, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD in a cohort of Chilean MSUD patients by identifying point mutations in the BCKDHA, BCKDHB, and DBT genes and to describe their impact on the phenotypic heterogeneity of these patients. METHODS: This manuscript describes a cross-sectional study of 18 MSUD patients carried out using PCR and DNA sequencing. RESULTS: Four novel pathogenic mutations were identified: one in BCKDHA (p.Thr338Ile), two in BCKDHB (p.Gly336Ser e p.Pro240Thr), and one in DBT (p.Gly406Asp). Four additional pathogenic mutations found in this study have been described previously. There were no correlations between the genotype and phenotype of the patients. CONCLUSION: If MSUD is diagnosed earlier, with a newborn screening approach, it might be possible to establish genotype-phenotype relationships more efficiently.
Asunto(s)
Enfermedad de la Orina de Jarabe de Arce/genética , Mutación , 3-Metil-2-Oxobutanoato Deshidrogenasa (Lipoamida)/genética , Aciltransferasas/genética , Niño , Chile , Dihidrolipoamida Deshidrogenasa/genética , Pruebas Genéticas/estadística & datos numéricos , Humanos , Enfermedad de la Orina de Jarabe de Arce/patologíaRESUMEN
Resumen Introducción: El bisfenol A (BPA) es un contaminante químico no persistente que altera el funcionamiento normal del sistema endocrino. Se sugiere que la exposición prenatal a BPA se asocia con la obesidad en la descendencia. Objetivo: Revisar la literatura sobre la exposición al BPA en mujeres embarazadas y su relación con la obesidad en sus hijos. Metodología: Revisión sistemática de acuerdo a la guía PRISMA, donde se realizaron búsquedas en las bases de datos Pubmed, ScienceDirect, Clinical Key, Medline, Ebsco y Scielo y el motor de búsqueda Google Scholar hasta 30 de abril de 2017 por dos investigadores independientes que utilizaron iguales términos de búsqueda. Se incluyeron estudios prospectivos de cohorte realizados que midieron el BPA en la orina materna. Resultados: Se incluyeron 5 estudios con tamaños de muestra que varían entre 297 y 757 binomios madre e hijo, se encontró asociación positiva entre la exposición prenatal a BPA con la circunferencia de cintura en niños de cuatro años β: 0.28 (IC95%:0.01 a 0.57) y el índice de masa grasa β: 0.31 (IC95%: 0.01 a 0.60) en dos de los estudios. Además, se observaron asociaciones positivas y/o negativas no significativas con índice de masa corporal y su puntaje Z, porcentaje de grasa, sobrepeso/obesidad, peso y talla al nacer, porcentaje de masa grasa. Conclusión: Los resultados del cuerpo existente de estudios epidemiológicos de cohorte, limita las afirmaciones sobre un vínculo causal entre la exposición prenatal BPA y la obesidad postnatal.
Abstract Introduction: Bisphenol A (BPA) is a non-persistent chemical pollutant which alters the normal functioning of the endocrine system. It is suggested that prenatal exposure is related to descendant obesity. Objective: Review literature on pregnant women's exposure to BPA and the relation to their children's obesity. Methodology: Systematic review in accordance with PRISMA guidelines. Searches were conducted on databases including Pubmed, ScienceDirect, Clinical Key, Medline, Ebsco and Scielo and Google Scholar search engine until April 30, 2017 by two independent researchers that used the same search terms. Prospective cohort conducted studies were included because they measured BPA in maternal urine. Results: Five studies were included with sample sizes ranging from 297 to 757 mother-child binomials. The review found a positive association between prenatal BPA exposure with 4-year-old children's waist circumference β: 0.28 (95% CI :0.01 to 0.57) and the fat mass index β: 0.31 (95%CI: 0.01 to 0.60) in two of the studies. non-significant positive and/or negative associations where observed with body mass index z-scores, overweight/ obesity, weight and size at birth, body mass percentage. Conclusion: The results of cohort epidemiological studies constrain statements regarding a causal link between prenatal BPA exposure and postnatal obesity.
Resumo Introdução: O bisfenol A (BPA) é um contaminante químico não persistente que altera o funcionamento normal do sistema endócrino. Se sugere que a exposição pré-natal se associa com a obesidade na descendência. Objetivo: Revisar a literatura sobre a exposição ao BPA em mulheres engravidadas e a sua relação com a obesidade em seus filhos. Metodologia: Revisão sistemática de acordo com a guia PRISMA. Se realizaram pesquisas nas bases de dados Pubmed, ScienceDirect, Clinical Key, Medline, Ebsco e Scielo e o motor de pesquisa Google Scholar até o 30 de Abril de 2017 por dois investigadores independentes que utilizaram os mesmos termos de busca. Se incluíram estudos prospectivos de coorte realizados que calcularam o BPA na urina materna. Resultados: Se incluíram 5 estudos com tamanhos de amostra entre 297 e 757 binômios mãe e filho, se encontrou associação positiva entre a exposição pré-natal a BPA com a circunferência de cintura em meninos de quatro anos β: 0.28 (IC95%:0.01 a 0.57) e o índice de massa de gordura β: 0.31 (IC95%: 0.01 a 0.60) em dois dos estudos. Se enxergaram associações positivas e/ou negativas não significativas com índice de massa corporal e a sua pontuação Z, porcentagem de gordura, sobrepeso/obesidade, peso e dimensão ao nascer, porcentagem de massa de gordura. Conclusão: Os resultados de estudos epidemiológicos de coorte, limita as afirmações sobre um vínculo causal entre a exposição pré-natal BPA e a obesidade pós-natal.
RESUMEN
BACKGROUND: Classical Galactosemia (CG) is an inborn error of galactose metabolism caused by the deficiency of the galactose-1-phosphate uridyltransferase enzyme. It is transmitted as an autosomal recessive disease and is typically characterized by neonatal galactose intolerance, with complications ranging from neonatal jaundice and liver failure to late complications, such as motor and reproductive dysfunctions. Galactosemia is also heterogeneous from a molecular standpoint, with hundreds of different mutations described in the GALT gene, some of them specific to certain populations, reflecting consequence of founder effect. METHODS: This study reviews the main clinical findings and depicts the spectrum of mutations identified in 19 patients with CG, six with Duarte Galactosemia and one with type 2 Galactosemia in Brazil. Some individuals were diagnosed through expanded newborn screening test, which is not available routinely to all newborns. RESULTS: The main classical Galactosemia mutations reported to date were identified in this study, as well as the Duarte variant and seven novel mutations - c.2 T > C (p.M1T), c.97C > A (p.R33S), c.217C > T (p.P73S), c.328 + 1G > A (IVS3 + 1G > A), c.377 + 4A > C (IVS4 + 4A > C), c.287_289delACA (p.N97del) and c.506A > C (p.Q169P). This was expected, given the high miscegenation of the Brazilian population. CONCLUSIONS: This study expands the mutation spectrum in GALT gene and reinforces the importance of early diagnosis and introduction of dietary treatment, what is possible with the introduction of Galactosemia in neonatal screening programs.
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Galactosemias/genética , Galactosemias/patología , Mutación , UTP-Hexosa-1-Fosfato Uridililtransferasa/genética , Alelos , Secuencia de Bases , Brasil , ADN/química , ADN/aislamiento & purificación , ADN/metabolismo , Genotipo , Humanos , Lactante , Recién Nacido , Polimorfismo GenéticoRESUMEN
Os Erros Inatos do Metabolismo (EIM) vêm sendo cada vez mais identificados nos últimos anos. A preocupação com o diagnóstico precoce decorre do foco na prevenção de deficiências, especialmente a mental. Este estudo descritivo teve por objetivo verificar diagnósticos confirmados e modalidades de tratamento utilizadas de janeiro de 2000 a dezembro de 2008. Método: foi realizada busca ativa de casos confirmados nos serviços que atendem esse tipo doença: neurologia (neuropediatria e doençasneuromusculares), pediatria (serviço de gastrologia e hepatologia) e genética clínica, além de levantamento no Serviço de Arquivo Médico do HCFMRP-USP. Foram confirmados 165 pacientes com EIM, com idades de um dia a 22 anos (mediana de um ano); 50 casos foram defeitos na síntese ou catabolismo de moléculas complexas, 65 no metabolismo intermediário, e 50 na produção ou utilização de energia. O tratamento foi instituído para 12 dos 50 pacientes do grupo I sendo reposição enzimática em 11 e transplante de medula óssea em um; todos do grupo II e III receberam orientação nutricional; 60 do grupo II receberam fórmula dietética industrializada; dos 50 do grupo III, 43 com mitocondriopatias receberam L-carnitina e coenzimas e aqueles com glicogenose, orientação sobre aporte de carbohidratos. A formação de novos recursos humanos, integração com a Rede EIM Brasil e linhas de pesquisa na área são prioridades para melhorar a acuidade na detecção e tratamento de erros inatos do metabolismo.
Inborn Errors of Metabolism have been increasingly identified in recent years. The early diagnosis focuses on prevention of disabilities, especially mental retardation. This descriptive study aims to verify confirmed diagnosis and treatment modalities in HCFMRP-USP cases from January of 2000 to December of 2008. A total of 165 patients with ages ranging from one day to 22 years (median one year) were detected. Fifty patients had synthesis or catabolism of complex molecules (group I), 65 intermediary metabolism (group II), and 50 had production or use of energy (group III) defects. Among the patients of group I, 11 had enzyme replacement therapy, and one bone marrow transplantation; for group II and III, inaddition to daily nutritional guidance for all of the patients, 60 from group II received industrialized diets; from group III, 43 with mitochondrial diseases received L-carnitine and coenzymes, and those with glycogenosis were focused mainly on the intake of carbohydrates. New human resources, integration with the Network EIM Brazil and lines of research in the area are priorities for improving the accuracy in the detection and treatment of inborn errors of metabolism.