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Renal cell carcinoma represents about 90% of all primary renal neoplasms. Clear cell renal cell carcinoma is the most common histological type, characterized by an aggressive clinical course due to its tendency to metastasize. Metastases are typically diagnosed on average 5 years after oncological surgery. Compared to metastasis to other organs, pancreatic metastases are rare. We present a case of clear cell renal carcinoma metastasis to the pancreas and liver, diagnosed 23 years after nephrectomy during the investigation of portal hypertension findings. Evaluating the late recurrence of clear cell renal carcinoma is crucial. There are no guidelines regarding the appropriate follow-up period after nephrectomy, and prospective studies may be useful in the future.
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We present a case of gastro-jejunal anastomotic stenosis due to the progression of malignant disease, successfully treated endoscopically by placing a lumen-apposing metal stent. This case illustrating the successful use of a lumen-apposing metal stent in a complex clinical scenario. This approach can significantly improve patient outcomes, especially in those who are poor surgical candidates or have advanced disease.
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Splenic artery pseudoaneurysm (SAP) is a rare and potentially life-threatening complication of pancreatitis, with a high risk of rupture and mortality rate. Early diagnosis and treatment are crucial, typically through endovascular approaches such as embolization. A 46-year-old woman with chronic pancreatitis experienced gastrointestinal bleeding from a ruptured SAP, which was successfully treated with embolization using hydrocoils, resulting in complete recovery.
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Carcinoid tumors are rare neoplasms, most frequently found in the gastrointestinal tract, responsible for the production of neuroendocrine mediators. Carcinoid syndrome is even rarer and consists of a set of symptoms characteristic of the release of these mediators into the systemic circulation. We present an interesting case of a patient with carcinoid syndrome as a late manifestation of a gastric neuroendocrine tumor with, highlighting the importance of knowing how to identify the carcinoid syndrome.
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Capsule endoscopy (CE) is considered the first-line for the investigation of OGIB after conventional non-diagnostic endoscopic examinations. A detection rate of lesions outside the small bowel segment has been reported to range from 3.5% to >30%. Our primary objective was to analyze the role of CE in identifying lesions outside the small bowel segment that were not identified on conventional endoscopy in patients suspected of OGIB. In our study, CE appears to be effective and safe in diagnosing OGIB, also proving to be a tool in identifying lesions outside the small intestine segment.
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BACKGROUND: Sickle Cell Disorder is Africa's most prevalent genetic disease. Yet, it remains a neglected condition, with high mortality under-five, and a lack of population-based studies in the region. This is the first of its kind in São Tomé e Príncipe, aiming to estimate the prevalence of sickle cell trait and other haemoglobin variants in women of reproductive age and its associated factors. METHODS: We conducted a cluster survey in 35 neighbourhoods. Haemoglobin was assessed through point-of-care capillary electrophoresis or high-performance liquid chromatography, and sociodemographic data through questionnaires. The weighted prevalence of sickle cell trait (HbAS) and HbC carriers was estimated with a 95% confidence interval (95% CI). We calculated weighted prevalence ratios (95% CI) through robust Poisson regression for its association with age and individual and collective genetic heritage. FINDINGS: The prevalence of sickle cell trait in women of reproductive age in São Tomé e Príncipe (n = 376) was 13.45% (95% CI: 9.05-19.00). The prevalence of HbC carriers was 8.00% (95% CI: 4.71-12.00). Older age and speaking Forro or Angolar were positively associated with having sickle cell trait. INTERPRETATION: The prevalence of sickle cell trait in São Tomé e Príncipe ranks high in the West African region. The country should follow international guidelines, implementing newborn screening and comprehensive healthcare management.
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Anemia Falciforme , Traço Falciforme , Recém-Nascido , Humanos , Feminino , Traço Falciforme/epidemiologia , Traço Falciforme/genética , Prevalência , Estudos Transversais , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , HemoglobinasRESUMO
Anorectal melanoma is a rare malignant tumor with the potential of simulating a benign anorectal disease, making its diagnosis difficult. We describe a case of anorectal melanoma, in which the interpretation of symptoms as hemorrhoidal disease delayed diagnosis and appropriate intervention.
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Esophagitis dissecans superficialis is an extremely rare benign illness. Although an association with medications, skin conditions, heavy smoking, and physical trauma has been reported, most cases remain unexplained. We present a previously healthy 42-year-old woman found to have EDS secondary to trauma. The patient started on PPI therapy with rapid and complete resolution of the endoscopic abnormality. This case shows the importance of identification of EDS, a rare and often underdiagnosed entity.
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INTRODUCTION: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme defect in the world, affecting more than 500 million people. In Portugal, the average frequency of G6PD deficiency in males was estimated at about 0.5% and since the year 2000 several G6PD-deficient alleles have been identified. The main goal of this study was to improve the knowledge on the molecular heterogeneity of G6PD deficiency in the Portuguese population. MATERIAL AND METHODS: A retrospective analysis of the mutational profile of 138 unrelated Portuguese individuals (101 males; 37 females), with no known sub-Saharan ancestry, who had been diagnosed with G6PD deficiency between 1994 and 2020 at the Molecular Hematology Unit of Centro Hospitalar e Universitário de Coimbra. The molecular study was done by direct Sanger sequencing or PCR-RFLP analysis. RESULTS: Twenty-one different pathogenic mutations were found. Among them, 20 were missense, causing the amino acid change, and one was an in-frame deletion in exon 10. The three most frequent mutations belong to the G6PD c.376A>G African background haplotype, namely the G6PD variants: A- (c.202G>A; p.68Val>Met) (58.6%), Betica (c.968T>C; p.323Leu>Pro) (12.1%) and Santamaria (c.542A>T; p.181Asp>Val) (4.3%). CONCLUSION: There is a wide molecular heterogeneity of G6PD deficiency in the Portuguese population.
Introdução: A deficiência de glicose-6-fosfato desidrogenase (G6PD) é o defeito enzimático mais comum no mundo, afetando mais de 500 milhões de pessoas. Em Portugal, a frequência populacional da deficiência de G6PD no sexo masculino foi estimada em cerca de 0,5%, e desde o ano 2000 têm vindo a ser descritas diversas variantes G6PD causadoras da deficiência. O principal objetivo deste estudo foi melhorar o conhecimento sobre a heterogeneidade molecular da deficiência de G6PD na população portuguesa.Material e Métodos: Análise retrospetiva do perfil mutacional de 138 indivíduos não-aparentados de naturalidade portuguesa (101 homens e 37 mulheres), sem ascendência subsaariana conhecida, diagnosticados com deficiência de G6PD entre 1994 e 2020 na Unidade de Hematologia Molecular do Centro Hospitalar e Universitário de Coimbra (CHUC). O estudo molecular foi feito por sequenciação direta de Sanger ou análise por PCR-RFLP.Resultados: Identificaram-se 21 mutações patogénicas diferentes. Destas, 20 são mutações missense, que levam à troca de aminoácido, e uma é uma deleção in-frame de 18 nucleótidos no exão 10. As três mutações mais frequentes pertencem ao haplótipo subsaariano G6PD c.376A>G, nomeadamente as variantes G6PD: A- (c.202G>A; p.68Val>Met) (58,6%), Betica (c.968T>C; p.323Leu>Pro) (12,1%) e Santamaria (c.542A>T; p.181Asp>Val) (4,3%).Conclusão: Existe uma elevada heterogeneidade molecular da deficiência de G6PD em Portugal.
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Deficiência de Glucosefosfato Desidrogenase , Masculino , Feminino , Humanos , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Glucosefosfato Desidrogenase/genética , Portugal , Estudos Retrospectivos , MutaçãoRESUMO
Congenital erythrocytosis (CE) represents a rare and heterogeneous group of hereditary disorders. The molecular basis of VHL gene mutations related to CE. Recently, Lenglet et al. reported a discovery of a novel cryptic exon in the VHL gene. Mutations in the first intronic region resulting in the creation of a cryptic exon termed E1' were found in seven families with CE and one family with VHL disease. We report three patients with prolonged CE with the aetiology being clarified several years later by sequencing of intronic region 1 of the VHL gene. This work addresses the first cases reported at the clinical level of VHL-associated CE due to the E1' cryptic exon.
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In the already identified quantitative trait loci (QTL), modulating Hb F levels are cis-acting haplotypes of the ß-globin gene cluster itself, although the single nucleotide polymorphisms (SNPs) accounting more for the association, remain uncertain. In this study, the role in Hb F production of previously reported candidate SNPs within the ß-globin gene cluster was reexamined, along with a yet poorly studied variation in the BGLT3 gene. In a sample of ß-thalassemia (ß-thal) carriers, we succeeded in replicating the significant association between increased Hb F levels and rs7482144 (C>T) (HBG2 XmnI), which is the most well-established variation in the cluster influencing the trait. This SNP was found to be in strong linkage disequilibrium (LD) with a variation in the HBBP1 gene [rs10128556 (G>A)], which consistently revealed a similar association signal. Remarkably, much stronger than the latter associations were those involving both rs968857 (T allele) (3' HBBP1) and rs7924684 (G allele) (BGLT3), two SNPs that were also in strong LD. As the pattern of LD detected in the ß-globin gene cluster does not correlate with a tight linkage between markers, complex interactions between SNPs at the cluster seem to modulate Hb F. Seeing that no such associations were detected in normal subjects, the question can be raised on whether, under erythropoiesis stress, epigenetic mechanisms contribute to change the regulation of the entire ß-globin gene cluster. In conclusion, we provide statistical evidence for a new player within the ß-globin gene cluster, BGLT3, that in cooperation with other regions influences Hb F levels in ß-thal carriers.
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Globinas beta , Talassemia beta , Proteínas de Transporte/genética , Hemoglobina Fetal/genética , Humanos , Família Multigênica , Locos de Características Quantitativas , Globinas beta/genética , Talassemia beta/genéticaRESUMO
Hb F production is under the influence of major quantitative trait loci (QTL). The present study aims: i) to replicate the association with Hb F for representative genetic variants in the three major Hb F QTLs in a Portuguese sample of ß-thalassemia (ß-thal) carriers; and ii) to test different genetic multi-locus models to account for the genetic component of Hb F variation. A population sample of 79 Portuguese ß-thal carriers (39 males, 40 females), aged between 2 to 70 years old, were genotyped for polymorphisms in the locus control region (LCR)-5' hypersensitive site 4 (5'HS4) rs16912979, XmnI-HBG2 rs7482144, BCL11A rs1427407 and HMIP rs66650371, using standard biomolecular procedures. Univariate linear regression models were used to test for genetic associations with Hb F. The minor alleles of the individual variants BCL11A rs1427407 (T) (0.165), HMIP rs66650371 (3 bp del) (0.247) and XmnI-HBG2 rs7482144 (T) (0.196), were found to be significantly associated with increased levels of Hb F (p = 0.029, p = 0.002 and p = 0.0004, respectively), explaining about 6.0, 12.0 and 15.0% of Hb F variation, respectively. In a multiple linear regression approach, the three loci accounted for about 30.0% of Hb F variance. Two genetic risk scores (GRS), rationalizing the number of minor alleles into a single genetic variable, explained about 30.0 and 32.0% of the Hb F variation. In conclusion, we replicated in ß-thal carriers previously reported associations with Hb F. Multi-locus models combining three representative variants of Hb F influencing QTLs can explain a larger amount of Hb F variability.
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Hemoglobina Fetal/genética , Talassemia beta/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Frequência do Gene , Variação Genética , Humanos , Região de Controle de Locus Gênico , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Portugal/epidemiologia , Locos de Características Quantitativas , Adulto Jovem , Talassemia beta/epidemiologiaRESUMO
INTRODUCTION: A burn disaster is defined by a mass casualty involving a large number of severely burned victims. Several countries have been confronted with these mass casualties and have developed national burn practice guidelines. This study presents a comprehensive review of the literature related to the benefits and conditions required for the introduction of a burn plan and identify successful strategies in Europe to apply in Portugal. METHODS: This study uses a scoping review approach, following the "five stages framework" suggested by Arksey and O'Malley (2005). A literature search strategy was designed to identify the relevant publications from three medical databases (PubMed/Medline, ScienceDirect, Scopus). Studies meeting our inclusion criteria were analyzed in detail. Data analysis included a descriptive summary and a thematic analysis. RESULTS: The research revealed that since 2000, 67 articles have been published on the subject. Of these 67 articles, only eight refer to burn plans in Europe. The papers which were included and reviewed were descriptive studies (N = 2), research paper (N = 2), reviews (N = 3), and an editorial (N = 1). Countries with published articles were Switzerland, Sweden, the Netherlands, and the United Kingdom. CONCLUSIONS: The research has shown a gap in the planning for major burn disasters in Europe. Although it is a very specific issue, and many times the approach to major disasters is carried out in a generalist way, the truth is that a burn disaster entails particularities that justify its unique approach. Since year 2000, only eight articles have been published in Europe and there are few publications showing intervention plans already tested and validated on the ground. In Portugal, there were no articles published that approaches this problem, making the rational of this work.
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Queimaduras , Planejamento em Desastres , Desastres , Incidentes com Feridos em Massa , Europa (Continente) , HumanosRESUMO
Glucose-6-phosphate isomerase (GPI) deficiency cause hereditary nonspherocytic hemolytic anemia (HNSHA) of variable severity in individuals homozygous or compound heterozygous for mutations in GPI gene. This work presents clinical features and genotypic results of two patients of Portuguese origin with GPI deficiency. The patients suffer from a mild hemolytic anemia (Hb levels ranging from 10 to 12.7g/mL) associated with macrocytosis, reticulocytosis, hyperbilirubinemia, hyperferritinemia and slight splenomegaly. Genomic DNA sequencing revealed in one patient homozygosity for a new missense mutation in exon 3, c.260G>C (p.Gly87Ala), and in the second patient compound heterozygosity for the same missense mutation (p.Gly87Ala), along with a frameshift mutation resulting from a single nucleotide deletion in exon 14, c.1238delA (p.Gln413Arg fs*24). Mutation p.Gln413Arg fs*24 is the first frameshift null mutation to be described in GPI deficiency. Molecular modeling suggests that the structural change induced by the p.Gly87Ala pathogenic variant has direct impact in the structural arrangement of the region close to the active site of the enzyme.
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Anemia Hemolítica Congênita não Esferocítica/genética , Mutação da Fase de Leitura , Glucose-6-Fosfato Isomerase/genética , Mutação de Sentido Incorreto , Domínio Catalítico , Humanos , Modelos Moleculares , Portugal , Conformação Proteica , Análise de Sequência de DNARESUMO
We herein present a case of congenital erythrocytosis caused by haemoglobin (Hb) Bethesda in a Japanese family. A 55-year-old asymptomatic man was referred to our hospital for the investigation of erythrocytosis, which was present in other members of his family. The patient's serum erythropoietin level was normal, and the JAK2 V617F mutation was not detected. His P50 value was mildly decreased, thus we suspected the presence of an Hb variant with a high oxygen affinity. The high-performance liquid chromatography analysis showed an abnormal Hb, and by direct sequencing we identified the Hb Bethesda variant in this patient. For the differential diagnosis, we recommend the estimation of the P50 value as a practical and useful test.
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Hemoglobinas Anormais/análise , Policitemia/congênito , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Policitemia/sangue , Policitemia/diagnósticoRESUMO
Three major loci have been associated with HbF levels, including -158C/T (XmnI) at HBG2 promoter region, and several polymorphisms at BCL11A intron-2 and HBS1L-MYB (HMIP) intergenic region. Mutations in the KLF1 gene were recently associated with increased HbF levels. This study aims to evaluate whether genetic variability at these loci influences HbF levels in ß-thalassemia carriers and in normal individuals of Portuguese origin. Sixty five ß-thalassemia carriers, HbF levels ranging from 0.2% to 9.5%, and 60 individuals with normal hematological parameters, HbF levels ranging from 0.2% to 7.4%, were selected for this study. In ß-thal carriers linear regression models revealed a strong statistical significant association for HBG2 (XmnI) rs7482144 (ß=0.455; P=5.858×10(-7)), and nominal significance for BCL11A rs766432 (ß=0.215; P=0.029) and HMIP rs9399137 (ß=0.209; P=0.011). In normal individuals, a case (HbF>2%; n=15) vs. control (HbF<1.7%; n=45) model, showed nominal significant associations for BCL11A SNPs rs11886868 (OR=4; P=0.001), rs766432 (OR=3.7; P=0.002) and rs7606173 (OR=0.36; P=0.032). KLF1 rs3817621 was not found associated with HbF levels. Our results suggest that in Portuguese ß-thal carriers the HBG2 XmnI polymorphism is strongly associated with HbF levels. In normal individuals, BCL11A polymorphisms, but not HMIP or HBG2 (XmnI) loci, are nominally associated with HbF expression.
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Proteínas de Transporte/genética , Hemoglobina Fetal/genética , Genoma Humano , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Talassemia beta/genética , gama-Globinas/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Proteínas de Ligação ao GTP/genética , Loci Gênicos , Estudo de Associação Genômica Ampla , Proteínas de Choque Térmico HSP70/genética , Heterozigoto , Humanos , Fatores de Transcrição Kruppel-Like/genética , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Mutação , Fatores de Alongamento de Peptídeos/genética , Portugal , Proteínas Proto-Oncogênicas c-myb/genética , Proteínas Repressoras , Talassemia beta/diagnóstico , Talassemia beta/patologiaRESUMO
Congenital erythrocytosis (CE), or congenital polycythemia, represents a rare and heterogeneous clinical entity. It is caused by deregulated red blood cell production where erythrocyte overproduction results in elevated hemoglobin and hematocrit levels. Primary congenital familial erythrocytosis is associated with low erythropoietin (Epo) levels and results from mutations in the Epo receptor gene (EPOR). Secondary CE arises from conditions causing tissue hypoxia and results in increased Epo production. These include hemoglobin variants with increased affinity for oxygen (HBB, HBA mutations), decreased production of 2,3-bisphosphoglycerate due to BPGM mutations, or mutations in the genes involved in the hypoxia sensing pathway (VHL, EPAS1, and EGLN1). Depending on the affected gene, CE can be inherited either in an autosomal dominant or recessive mode, with sporadic cases arising de novo. Despite recent important discoveries in the molecular pathogenesis of CE, the molecular causes remain to be identified in about 70% of the patients. With the objective of collecting all the published and unpublished cases of CE the COST action MPN&MPNr-Euronet developed a comprehensive Internet-based database focusing on the registration of clinical history, hematological, biochemical, and molecular data (http://www.erythrocytosis.org/). In addition, unreported mutations are also curated in the corresponding Leiden Open Variation Database.
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Bases de Dados Genéticas , Predisposição Genética para Doença , Mutação , Policitemia/congênito , Receptores da Eritropoetina/genética , Hipóxia Celular/genética , Eritropoetina/metabolismo , Humanos , Internet , Policitemia/genética , Policitemia/metabolismo , Transdução de Sinais/genéticaRESUMO
INTRODUCTION: Congenital erythrocytosis can be classified as primary, when the defect is intrinsic to the RBC progenitors and independent of the serum erythropoietin (Epo) concentration, or secondary, when the erythrocytosis is the result of an upregulation of Epo production. Primary erythrocytosis is associated with mutations in the EPOR gene, secondary CE can de due to mutations that stabilize the hemoglobin in the oxygenated form or to mutations in the genes that control the transcriptional activation of the EPO gene - VHL, EGLN1, EPAS1. Chuvash polycythemia, caused by mutations in VHL gene, shares features of both primary and secondary erythrocytosis, with increased Epo production but also hypersensitivity of progenitors to Epo. MATERIAL AND METHODS: With the main objective of describing the etiology and molecular basis of CE, we have studied 70 consecutive unrelated patients presenting with idiopathic erythrocytosis from our hematology clinic or referred from other centers. According to a study algorithm, we have sequenced all the genes described as associated with CE. RESULTS AND DISCUSSION: Erythrocytosis molecular etiology was identify in 25 (36%) of the 70 subjects. High-affinity Hb variants were the most common cause, present in 20% of the cases. New mutations were identified in the JAK2, EPOR, VHL, and EGLN1 genes. CONCLUSIONS: High-affinity hemoglobin variants are a very rare cause of secondary CE, but it seems likely that their incidence may be underestimated. Our experience shows that in erythrocytosis with a dominant inheritance and normal or inappropriate high Epo levels, the HBB and HBA genes should be the first to be studied. In spite of the seven genes known to be involved in CE, the majority of the cases have unknown etiology.