Fabry disease is an X-linked lysosomal storage disease due to alpha-galactosidase A (α-Gal A) deficient activity which leads to the accumulation of glucoesphingolipids, such as globotriaosilceramide. There are over 700 known mutations of the enzyme gene, and most of them cause Fabry Disease. This case report describes a hemodialysis patient with a rare and controversial GLA gene mutation, the D313Y. The medecial investigation confirmed that D313Y is an alpha-galactosidase A sequence variant that causes pseudo deficient enzyme activity in plasma but not Fabry disease. Thus, clinical symptoms that prompted Fabry disease investigation could not be attributable to Fabry disease and therefore enzyme replacement therapy was not indicated.
Introduction: Nephroblastoma or Wilms' tumor is the most frequent renal cancer in children. Although its prognosis is favorable for most patients, it may relapse or have a fatal outcome. The characterization of risk groups by applying immunohistochemical biomarkers aims to adapt the treatment to its corresponding group as well as to reduce relapses and fatal outcome. p53, B-cell lymphoma 2 (BCL-2), BCL-2 associated protein X (BAX) and vascular endothelial growth factor receptor 1 (VEGFR1) are among the most widely studied biomarkers, which are related to the apoptotic pathway, DNA repair and neovascularization. Objective: The objective of this study is to assess the immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 in samples of human nephroblastoma and to correlate them with clinicopathological prognostic factors. Material and methods: Twenty-nine surgical specimens of nephroblastoma diagnosed from 1994 to 2007 were selected from the Anatomopathological Service of two hospitals in Curitiba. The immunohistochemical analysis of tissue microarrays was performed through immunoperoxidase staining and the yielded results were compared with clinicopathological prognostic factors. Results: The major immunohistochemical expression of VEGFR1 in blastema and epithelium presented positive association with the risk group. Hence this may be related to higher vascular neoplastic invasion apparently caused by the endothelial growth factor, which maximizes the chances of metastasis and ultimately changes tumor staging, risk group and clinical evolution. Conclusions: The immunohistochemical expression of VEGFR1 substantiated a directly proportional association with the nephroblastoma risk group.
RESUMOO fosfato (Pi) é um mineral essencial que participa de diversos processos metabólicos, como produção de energia e sinalização intracelular, além de ser um importante constituinte de diversos elementos celulares. A homeostase do Pi, estritamente regulada pelo paratormônio, pela vitamina D e pelo fator de crescimento fibroblástico -23, sofre um grande desequilíbrio com a perda da função renal, culminando com o desenvolvimento de hiperfosfatemia. Nessa revisão abordaremos a fisiologia do Pi e o seu desequilíbrio causado pela disfunção renal, que se revela através do desenvolvimento da sobrecarga de Pi e da própria hiperfosfatemia. Discutiremos ainda as principais evidências clínicas e experimentais que apontam para o Pi como o mais novo vilão das doenças cardiovasculares tanto na população renal crônica quanto na geral. As estratégias terapêuticas devem ser voltadas sobretudo para a redução da ingestão de Pi, que encontra-se aumentada nos dias atuais devido a presença de conservantes à base desse elemento utilizados nos alimentos industrializados. Estudos populacionais são urgentemente necessários para testar de modo mais amplo os possíveis efeitos benéficos do controle da sobrecarga de Pi sobre o sistema cardiovascular.Palavras chave: Fosfato; Doença Cardiovascular ABSTRACT Phosphate is an essential intracellular mineral that plays its role in a variety of metabolic pathways, like energy production and intracellular synthetis, apart from being and important block to various intracellular elements. Homeostasis of Pi, strictly regulated by parathormone, vitamin D and fibroblast growth factor 23, suffers greatly by the decline of renal function, as seen when phosphate overload and hyperphosphatemia takes its place. We will discuss the major clinical and experimental evidence that points to Pi as the newest villain of cardiovascular disease in the chronic renal disease population, as well as the population in general. Therapeutic strategies should be directed mainly in the reduction of Pi intake, that finds itself increased nowadays due to the presence of food preservatives based on this element in industrialized food. Populational studies are urgently needed to test in a more broad way the possible benefic effects of Pi overload control on cardiovascular system.
Introduction and Aims: Fabry disease is an X-linked lysosomal storage disease that is caused by deficient activity of lysosomal enzyme α -galactosidase A. It leads to deposition of glycosphingolipids, mainly globotriaosylceramide, resulting in varying degrees of organ dysfunction, such as chronic kidney disease. The aim of the study was to evaluate the clinical evolution of Fabry nephropathy in a real-world medical practice condition. Methods: This is a retrospective study that evaluated Fabry disease patients followed in the outpatient Clinic Center for Fabry Disease in Tapejara -Brazil. Patients with baseline data on renal function (serum creatinine) and proteinuria prior to enzyme replacement therapy (ERT) were included. Glomerular filtration rate (GFR) was estimated based on the CKD-EPI formula. Renal function reduction was defined as a rise in serum creatinine > 25% from baseline. Clinical and laboratory data were collected from medical records. Fabry disease diagnosis was based on clinical and laboratorial manifestations as well as in the identification of the gene mutation. Results: Eighteen out of seventy-two Fabry disease patients were included: female gender 17/18, age 33.7 ± 15.3 (16 -57) years. Patients presented the following missense mutations: p.y365x (n=14; 78%), w47x (n=3;17%) or p.w204x (n=1;5%). Regarding renal data, serum creatinine 0.84 ± 0.2 mg/dl, eGFR 92.5 ± 26.7, proteinuria 353.9 ± 632.9 mg/24h at baseline. Four patients had chronic kidney disease (defined as eGFR ≤ 60 and/or albuminuria > 300 mg/24h). Acroparesthesia was present in 11 (61%) patients and angiokeratomas, hypohidrosis, hypoacusia, headache and depression were present each in one (5,5%) patient at Fabry's diagnosis. Fourteen patients had signs of left ventricular or interventricular septal hyperthrophy by magnetic nuclear ressonance. Only the male patient had first-degree atrioventricular block. The time between the diagnosis and initiation of ERT was 4.4 ± 3.5 (0 -14) years. The most frequent indication for ERT was Fabry nephropathy (67%). Renin-angiotensin system antagonists were used in all patients. Patients were followed-up up to 36 months. The eGFR and proteinuria remained stable or improved in 8 (44%) patients. Renal function did not worsen in any patient during the follow-up. Conclusions: Our preliminary results give support to the notion that ERT, in conjunction with blockage of renin angiotensin system, is an efficient strategy to prevent further deterioration and, in some instances, remission of Fabry nephropathy. Due to the design of the study, it was not possible to separate the benefit of each therapeutic strategy. Randomized controlled trials are expensive and their results cannot always be extrapolated to daily practice. Real life practice studies may broaden our insight into the treatment, particularly, in the case of rare diseases where patient recruitment and inclusion are hard to achieve.
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