Subject(s)
Hemochromatosis , Ventricular Dysfunction, Left , Female , Humans , Male , Middle Aged , Echocardiography/methods , Global Longitudinal Strain , Hemochromatosis/complications , Hemochromatosis/genetics , Hemochromatosis/diagnosis , Hemochromatosis/physiopathology , Hemochromatosis Protein/genetics , Homozygote , Ventricular Dysfunction, Left/etiology , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/diagnosis , AgedABSTRACT
Hemochromatosis (HC) is a disorder that alters the body's ability to metabolize iron, increasing its absorption, causing iron overload, and consequently an accumulation of the mineral in multiple organs such as the liver, heart, and pancreas. The amount of total iron in the body is 2-4 g in healthy individuals and remains within these limits throughout life thanks to the control of intestinal absorption. In patients with CH, this amount is increased by at least 10 times, which translates into body deposits of 20-40 grams of iron on average. Factors that increase the risk of having HC: having two copies of the mutated HFE gene, family history, ethnicity or ancestry from Northern Europe (less common in blacks, Hispanics, and Asians), and male gender.
Subject(s)
Humans , Middle Aged , Hemochromatosis/diagnosis , Hemochromatosis/physiopathology , Signs and Symptoms , Liver Transplantation , Heart Failure , Hemochromatosis/therapy , Hemosiderosis , IronABSTRACT
INTRODUCCIÓN: La hemocromatosis hereditaria, al provocar hiperferritinemia, puede tener el potencial de aumentar la capacidad aeróbica y el rendimiento deportivo en atletas. Sin embargo, diversos estudios afirman que la sobrecarga de hierro podría afectar negativamente al rendimiento físico y la función muscular. OBJETIVO: Recopilar y analizar evidencias sobre la relación entre la hemocromatosis hereditaria y el rendimiento deportivo. MÉTODO: Se realizó una revisión sistemática, de acuerdo a los estándares PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses), en las siguientes bases de datos: Scopus, Web of Science, PubMed y Dialnet. RESULTADOS: Tras aplicar los criterios de inclusión/exclusión, 13 artículos fueron incluidos y analizados. CONCLUSIONES: Existen variaciones en los genes que están relacionados con el estado de resistencia del atleta. Actualmente, el gen HFE no se sitúa entre los polimorfismos del ácido desoxirribonucleico que aumenten el rendimiento deportivo. Son mayoría las investigaciones en las que recalcan la necesidad de evaluar el estado de ingesta de hierro en el deportista
INTRODUCTION: Hereditary hemochromatosis, by causing hyperferritinemia, may have the potential to increase aerobic capacity and sports performance in athletes. However, various studies claim that iron overload could affect physical performance and muscle function negatively. OBJECTIVE: The aim of this review was to collect and analyze evidence on the relationship between hereditary hemochromatosis and sports performance. METHOD: A systematic review was carried out, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards, in the following databases: Scopus, Web of Science, PubMed and Dialnet. RESULTS: After applying the inclusion / exclusion criteria, 13 articles were included and analyzed. CONCLUSIONS: There are variations in the genes which are related to the aerobic capacity of the athletes. Currently, the HFE gene is not among the deoxyribonucleic acid polymorphisms that increase sports performance. The vast majority of the studies analyzed emphasize the need to assess the state of iron intake in athletes
INTRODUÇÃO: A hiperferritinemia associada à hemocromatose hereditária, pode apresentar o potencial de aumentar a capacidade aeróbica e o desempenho desportivo em atletas. Contudo, vários estudos afirmam que a sobrecarga de ferro pode afetar negativamente o desempenho físico e a função muscular. OBJETIVO: Recolher e analisar evidências referentes à relação entre hemocromatose hereditária e desempenho desportivo. MÉTODO: Revisão sistemática de acordo com os padrões PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) através das seguintes bases de dados: Scopus, Web of Science, PubMed e Dialnet. RESULTADOS: Após a aplicação dos critérios de inclusão / exclusão, 13 artigos foram incluídos e analisados. CONCLUSÕES: Existem variações nos genes que estão relacionados com o estado de resistência do atleta. Atualmente, o gene HFE não está entre os polimorfismos de ácido desoxirribonucleico que aumentam o desempenho desportivo. A maioria dos estudos enfatiza a necessidade de avaliar o estado de ingestão de ferro em atletas
Subject(s)
Humans , Hemochromatosis/physiopathology , Exercise/physiology , Motor Activity/physiology , Hepcidins/therapeutic use , Hepcidins/metabolism , Athletic PerformanceABSTRACT
No disponible
Subject(s)
Humans , Male , Female , Infant, Newborn , Hemochromatosis/therapy , Early Diagnosis , Hemochromatosis/diagnosis , Hemochromatosis/physiopathology , Retrospective Studies , ImmunohistochemistryABSTRACT
La hemocromatosis neonatal es la causa más frecuente de fallo hepático agudo en el periodo neonatal. Asocia una elevada morbimortalidad dado el daño hepático secundario a acúmulo de hierro. En los últimos años, las nuevas evidencias acerca de su etiopatogenia aloinmune han repercutido sobre el diagnóstico, el tratamiento y el pronóstico de estos pacientes. El tratamiento con gammaglobulinas y exsanguinotransfusión ha cambiado radicalmente el pronóstico libre de trasplante. Otro gran éxito ha sido el uso preventivo de gammaglobulina en las gestantes con antecedentes de hemocromatosis neonatal, disminuyendo así la tasa de recurrencia de la enfermedad de hasta un 70%. Este nuevo paradigma ha convertido a una entidad con un pobre pronóstico en una patología con posibilidad de curación si se diagnostica y trata precozmente. A pesar de ello, sigue habiendo un gran desconocimiento generalizado de la enfermedad, con implicaciones médicas que derivan en un importante problema sanitario, ya que estos pacientes se derivan de forma tardía a los centros especializados
Neonatal hemochromatosis is the most common cause of acute liver failure in the neonatal period. It is associated with high morbidity and mortality due to iron overload in hepatic and extra-hepatic tissues. New evidence has emerged during the last few years as regards its alloimmune etiology, which have had an important repercussion on the diagnosis, treatment and prognosis of these patients. Treatment with immunoglobulins and exchange transfusions has radically changed the prognosis without liver transplant. Another great success has been the preventive use of immunoglobulin in pregnant women with a past history of neonatal hemochromatosis, thus decreasing the rate of disease recurrence up to 70%. This new paradigm has led to an entity with a poor prognosis becoming a curable disease if diagnosed and treated early. Nevertheless, a large widespread ignorance of the disease persists, with medical implications that result in significant health problems, due to the delayed referral of these patients to specialized centers
Subject(s)
Female , Humans , Infant, Newborn , Male , Hemochromatosis/diagnosis , Hemochromatosis/physiopathology , Hemochromatosis/therapy , Hemochromatosis/prevention & control , Liver Failure/diagnosis , Liver Failure/etiology , Iron/metabolism , gamma-Globulins/therapeutic use , Platelet Transfusion , Infant, Newborn, Diseases , Recurrence , Immunization, Passive , Liver Transplantation , Pregnancy ComplicationsABSTRACT
La hepatitis aloinmune fetal, conocida anteriormente como hemocromatosis neonatal, ha demostrado en los últimos años ser una enfermedad completamente distinta a la hemocromatosis del adulto, tanto en su etiología como en su la fisiopatología. Este conocimiento abre nuevas perspectivas tanto en la prevención de la enfermedad en futuros embarazos, así como en el tratamiento con inmunoglobulina endovenosa en la madre durante el embarazo y eventualmente el tratamiento postnatal, en el que el trasplante de hígado juega un rol primordial.
Fetal alloimmune hepatitis, until few years ago was known as neonatal hemochromatosis, has shown to be a completely different disease from hemochromatosis in the adult, in its etiology and pathophysiology. This knowledge opens up opportunities of counselling in future pregnancies as well as in the treatment with intravenous immunoglobulin to the mother during pregnancy, and eventually the postnatal treatment, in which liver transplantation plays a primary role.
Subject(s)
Humans , Female , Pregnancy , Infant, Newborn , Fetal Diseases/immunology , Hemochromatosis/diagnosis , Hemochromatosis/immunology , Hemochromatosis/therapy , Prognosis , Liver Transplantation , Immunoglobulins, Intravenous/therapeutic use , Diagnosis, Differential , Hemochromatosis/physiopathologyABSTRACT
La hemocromatosis hereditaria es un trastorno genético. En los últimos años se ha profundizado en el conocimiento de su fisiopatología y diagnóstico. Estos síndromes se caracterizan por sobrecarga de hierro y se distinguen varios subtipos de acuerdo con la mutación existente. Dentro de ellas, las mutaciones en el gen HFE o hemocromatosis hereditaria tipo I es la más común. Esta enfermedad tiene una gran morbilidad y mortalidad asociada a la sobrecarga del mineral. Se presentan 4 pacientes en los que por primera vez en Cuba se identificaron las mutaciones del gen HFE
Hereditary hemochromatosis is a genetic disorder. Detailed studies on its physiopathology and diagnosis have been carried out over the last years. The syndromes are characterized by iron overload and several subtypes are distinguished according to the existing mutation. Among them, the mutations in HFE gene or hereditary hemochromatosis type I is the most common. This disease has a great morbidity and mortality associated to mineral overload. For the first time in Cuba, we report four patients with confirmed mutations in HFE genes
Subject(s)
Humans , Hemochromatosis/diagnosis , Hemochromatosis/physiopathology , Mutation/genetics , Case-Control StudiesABSTRACT
La hemocromatosis hereditaria es un trastorno genético. En los últimos años se ha profundizado en el conocimiento de su fisiopatología y diagnóstico. Estos síndromes se caracterizan por sobrecarga de hierro y se distinguen varios subtipos de acuerdo con la mutación existente. Dentro de ellas, las mutaciones en el gen HFE o hemocromatosis hereditaria tipo I es la más común. Esta enfermedad tiene una gran morbilidad y mortalidad asociada a la sobrecarga del mineral. Se presentan 4 pacientes en los que por primera vez en Cuba se identificaron las mutaciones del gen HFE(AU)
Hereditary hemochromatosis is a genetic disorder. Detailed studies on its physiopathology and diagnosis have been carried out over the last years. The syndromes are characterized by iron overload and several subtypes are distinguished according to the existing mutation. Among them, the mutations in HFE gene or hereditary hemochromatosis type I is the most common. This disease has a great morbidity and mortality associated to mineral overload. For the first time in Cuba, we report four patients with confirmed mutations in HFE genes(AU)
Subject(s)
Humans , Hemochromatosis/diagnosis , Hemochromatosis/physiopathology , Mutation/genetics , Case-Control StudiesABSTRACT
FUNDAMENTO: Pacientes com talassemia major (TM) apresentam hemólise crônica e necessitam de transfusões sanguíneas egularmente que podem causar cardiomiopatia por sobrecarga de ferro e insuficiência cardíaca crônica. A hemocromatose é caracterizada por acúmulo excessivo de ferro nos tecidos; acometimento do coração é a principal causa de óbito em pacientes com talassemia. OBJETIVO: Avaliar as estruturas e a função cardíaca por meio de ecocardiografia com Doppler convencional e Doppler tecidual em pacientes com TM, sem evidência clínica de insuficiência cardíaca. MÉTODOS: Trata-se de estudo observacional prospectivo de 18 pacientes com TM que recebem transfusão sanguínea regularmente. Para avaliar, separadamente, os efeitos da anemia e da transfusão sanguínea, dois grupos controles pareados por gênero, idade, peso e altura foram incluídos: um com indivíduos saudáveis (Saudável, n = 18) e outro com pacientes com anemia por deficiência de ferro (Anemia, n = 18). Análise estatística foi realizada utilizando ANOVA seguida pelo teste de Tukey ou Kruskal-Wallis e teste de Dunn. RESULTADOS: As seguintes variáveis ecocardiográficas apresentaram valores significativamente mais elevados no grupo TM do que nos grupos Anemia e Saudável: índice de volume do átrio esquerdo (Saudável: 16,4 ± 6,08; Anemia: 17,9 ± 7,02; TM: 24,1 ± 8,30 cm/m); razão E/Em septal mitral (Saudável: 6,55 ± 1,60; Anemia: 6,74 ± 0,74; TM: 8,10 ± 1,31) e duração do fluxo reverso em veias pulmonares [Saudável: 74,0 (59,0-74,0); Anemia: 70,5 (67,0-74,0); TM: 111 (87,0-120) ms]. Arazão E/A mitral foi maior no grupo TM do que no grupo Anemia (Saudável: 1,80 ± 0,40; Anemia: 1,80 ± 0,24; TM: 2,03 ± 0,34). Não foram encontradas diferenças entre os grupos em variáveis estruturais do ventrículo esquerdo e em índices de função sistólica. CONCLUSÃO: A ecocardiografia com Doppler convencional e o Doppler tecidual permite que alterações na função diastólica do ventrículo esquerdo sejam identificadas em pacientes assintomáticos com talassemia major.
BACKGROUND: Patients with thalassemia major present chronic hemolysis and require regular blood transfusions which may cause iron overload cardiomyopathy and chronic heart failure. Hemochromatosis is characterized by excessive iron accumulation in tissues, and heart involvement is the main cause of death in patients with thalassemia. OBJECTIVE: The aim of this study was to evaluate cardiac structure and function by conventional Doppler echocardiography and tissue Doppler imaging in patients with TM and no clinical evidence of heart failure. METHODS: This is a prospective observational study including 18 patients with thalassemia major (TM) receiving regular blood transfusion. To separately evaluate anemia and blood transfusion effects, two gender, age, weight, and height-matched control groups were included: one with healthy individuals (Healthy, n=18) and one with iron deficient anemia patients (Anemia, n=18). Statistical analysis was performed using ANOVA followed by Tukey's test or Kruskal-Wallis's and Dunn's test. RESULTS: The following echocardiographic variables presented significantly higher values in TM than the Anemia and Healthy groups: left atrium volume index (Healthy: 16.4±6.08; Anemia: 17.9±7.02; TM: 24.1±8.30 cm³/m²); mitral septal E/Em ratio (Healthy: 6.55±1.60; Anemia: 6.74±0.74; TM: 8.10±1.31); and duration of reverse pulmonary vein flow [Healthy: 74.0 (59.0-74.0); Anemia: 70.5 (67.0-74.0); TM: 111 (87.0-120) ms]. The mitral E/A ratio was higher in TM than Anemia (Healthy: 1.80±0.40; Anemia: 1.80±0.24; TM: 2.03±0.34). No differences were found in left ventricular structures and systolic function indexes. CONCLUSION: Conventional Doppler echocardiography and tissue Doppler allow changes in left ventricular diastolic function to be identified in asymptomatic patients with thalassemia major.
Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Young Adult , Blood Transfusion/adverse effects , Chelation Therapy , Echocardiography, Doppler/methods , Iron Chelating Agents/therapeutic use , Ventricular Function , beta-Thalassemia/complications , Age Factors , Anemia/etiology , Anemia/physiopathology , Epidemiologic Methods , Hemodynamics , Hemochromatosis/etiology , Hemochromatosis/physiopathology , Hemolysis/physiology , Sex Factors , beta-Thalassemia/physiopathology , beta-Thalassemia/therapyABSTRACT
La hemocromatosis hereditaria es el trastorno genético más común en la población caucásica, con una prevalencia estimada de 1/200-1/400 (homocigotos) y de 1/8-1/10 en portadores (heterocigotos). Tiene una transmisión de carácter recesivo y ligado al HLA. La expresión clínica de la enfermedad aparece solo en homocigotos y va depender del momento del diagnóstico y del grado de afectación orgánica. El caso clínico a continuación presentamos describe el proceso del diagnóstico diferencial realizado en un paciente joven con coxartosis unilateral, y sospecha clínica de hemocromatosis. El diagnóstico precoz de la hemocromatosis hereditaria en atención primaria, puede disminuir la morbimortalidad de esta enfermedad al detectar homocigotos en edades tempranas (AU)
Hereditary haemochromatosis is the most common genetic disorder in the Caucasian population, with an estimated prevalence of 1/200-1/400 (homozygous) and 1/8-1/10 in carriers (heterozygous). The transmission is recessive and linked to HLA. The clinical expression of disease appears only in homozygous and will depend on the time of diagnosis and the degree of organ involvement. The clinical case presented below describes the process of differential diagnosis made in a young patient with unilateral coxarthrosis and clinical suspicion of hemochromatosis. Early diagnosis of hereditary hemochromatosis in primary care can reduce morbidity and mortality of this disease by detecting homozygous at younger ages (AU)
Subject(s)
Humans , Male , Adult , Osteoarthritis, Hip/complications , Osteoarthritis, Hip/diagnosis , Hemochromatosis/complications , Hemochromatosis/diagnosis , Primary Health Care/methods , Primary Health Care , Diagnosis, Differential , Osteoarthritis, Hip/physiopathology , Osteoarthritis, Hip , Hemochromatosis/physiopathology , Hemochromatosis , Primary Health Care/trends , Hip/pathology , Hip , Mass Screening/methods , AbdomenABSTRACT
Objective: To study lesions in the oral cavity of patients with hereditary hemochromatosis and determine their association with iron overload. Study Design: We took a clinical history, examined the pigmentation of the oral mucosa, and measured total stimulated saliva production. We correlated our results with epidemiological, phenotypic, and genotypic findings. Patients with associated diseases or drug therapy causing xerostomia were excluded. Results: We evaluated 25 patients (20 men, mean age 52 years) over a period of 6 months. No patient complained of xerostomia and pigmentation was not detected in the oral mucosa. The total stimulated salivary flow was reduced in 9 patients who had an average ferritin level of 796.5 ìg/l. The decline in total stimulated salivary flow was significantly correlated with ferritin levels (p=0.002). Patients with ferritin levels within the normal range also had normal stimulated salivary flow. Conclusions: We found no pigmented lesions in the oral mucosa; however, we did observe a decrease in total stimulated salivary flow that correlated with ferritin levels. Therefore, hyposialia caused by functional impairment of the salivary glands may be an early marker of iron deposition (AU)
Subject(s)
Humans , Hemochromatosis/physiopathology , Hyperpigmentation/epidemiology , Mouth Mucosa/physiopathology , Salivary Glands/physiopathology , Saliva , FerritinsABSTRACT
Fundamento y objetivo: La hiperferritinemia es un hallazgo común en la práctica clínica diaria que puede ser congénita o adquirida y no siempre se asocia con sobrecarga férrica. La hiperferritinemia genética puede acompañarse de sobrecarga, como en la hemocromatosis hereditaria, o cursar con cataratas sin sobrecarga, en ese caso es el síndrome hereditario de hiperferritinemia y cataratas. Por otra parte, el síndrome metabólico puede cursar con hiperferritinemia y sobrecarga leve-moderada pero sin aumento de saturación de transferrina. Presentamos una familia con hiperferritinemia.Pacientes y método: Estudio de una familia con hiperferritinemia dual, congénita y adquirida, con análisis de los genes implicados en el metabolismo del hierro. Resultados:Los pacientes con síndrome hereditario de hiperferritinemia y cataratas tienen la mutación c.-167C>T en heterocigosis en el gen FTL. El paciente con síndrome metabólico presenta, además, una nueva mutación en heterocigosis en el gen TFR2 (c.1259G>A, p.Arg420His). Conclusiones: La hiperferritinemia, habitualmente casual, supone para el clínico un reto diagnóstico por sus diversidades fenotípicas y genotípicas, siendo necesario aunar esfuerzos en investigación básica y clínica para la asistencia de los pacientes (AU)
Background and objetives: Hyperferritinemia is a common finding in clinical practice. This condition can be congenital or acquired, although it is not always associated with iron overload. Genetic hyperferritinemia is associated with iron overload, hereditary hemochromatosis, or cataracts that progress without iron overload (hereditary hyperferritinemia-cataract syndrome). Metabolic syndrome is associated with hyperferritinemia and mild iron overload, with no increase in transferrin saturation. We report a family with hyperferritinemia. Patients and methods: We present the study of a family with dual hyperferritinemia (congenital and acquired) and an analysis of the genes involved in iron metabolism. Results: Patients with hereditary hyperferritinemia-cataract syndrome have the mutation c.-167C>T in the FTL gene; patients with metabolic syndrome present a new mutation in the TFR2 gene (c.1259G>A, p.Arg420His).Conclusions: The phenotypic and genotypic diversity of hyperferritinemia makes it a diagnostic challenge for clinicians. Basic research and clinical research should be combined to ensure better patient care (AU)
Subject(s)
Humans , Hemochromatosis/physiopathology , 16595/complications , Metabolic Syndrome/complications , Ferritins , Cataract/congenital , Receptors, Transferrin/geneticsABSTRACT
A hemocromatose hereditária é caracterizada pelo aumento da absorção intestinal de ferro, acarretando progressivo acúmulo no organismo. Os objetivos foram: 1- determinar as frequências das mutações p.C282Y, p.H63D e p.S65C no gene HFE e avaliar os efeitos nas concentrações dos parâmetros do ferro em doadores de sangue; 2- pesquisar mutações nos genes: 2.1- HFE, 2.2- HJV e HAMP, 2.3- TFR2 e SLC40A1, em pacientes portadores de sobrecarga de ferro primária. Participaram 542 doadores de sangue provenientes do Hemocentro da Santa Casa de São Paulo. Foram incluídos 51 pacientes que apresentavam saturação de transferrina ≥ 50% (para mulheres) e ≥ 60% (para homens) e ausência de causas secundárias. Os genótipos para as mutações nos genes HFE foram avaliados pela PCR-RFLP. Foi realizado sequenciamento direto bidirecional para cada éxon dos genes, utilizando o sequenciador Genetic Analizer 3500XL®. Nos doadores de sangue, as frequências dos alelos HFE 282Y, HFE 63D e HFE 65C foram 2,1, 13,6 e 0,6%, respectivamente. Os homens que doaram pela primeira vez, portadores do genótipo HFE 282CY, apresentaram maiores valores de saturação de transferrina; e também os portadores dos genótipos HFE 63DD e 63HD apresentaram maiores concentrações de ferritina sérica, em relação aos de genótipo selvagem. Para os pacientes, 72,5% (37/51) apresentaram ao menos 1 alteração no gene HFE e 11 foram identificados como homozigotos para a mutação p.C282Y. Uma mutação não descrita na literatura (p.V256I) foi identificada no gene HFE e a modelagem molecular (análises de ligação e estrutural) detectou que a mutação não reduziu a afinidade entre as proteínas HFE e β2-microglobulina. No sequenciamento dos éxons dos genes HJV e HAMP foram identificadas as alterações já descritas: HJV p.E302K, HJV p.A310G, HJV p.G320V e HAMP p.R59G. Para o gene TFR2, foram identificados 3 polimorfismos já descritos (p.A75V, p.A617A e p.R752H). No gene SLC40A1 foram observados 6 polimorfismos (rs13008848, rs11568351...
Hereditary hemochromatosis (HH) is characterized by increased intestinal iron absorption, which leads to a progressive accumulation of iron in the body. The aims were: 1- to assess the frequency of HFE gene mutations (p.C282Y, p.H63D and p.S65C) and to identify their relationship to iron status in blood donors; 2- to search in primary iron overload patients: 2.1- HFE, 2.2- HJV and HAMP, 2.3- TFR2 and SLC40A1 gene mutations. Blood donors (n=542) were recruited from Hemocentro of Santa Casa Hospital, Sao Paulo, Brazil. The study included 51 patients with transferrin saturation ≥ 50% (women) and ≥ 60% (men) and absence of secondary causes. The genotypes for HFE mutations were evaluated by PCR-RFLP. Subsequent bidirectional sequencing for each gene was performed using the Genetic Analizer sequencer 3500XL®. The frequencies of HFE 282Y, HFE 63D and HFE 65C alleles were 2.1, 13.6 and 0.6% in blood donors, respectively. The first time male donors carrying heterozygous genotype for the p.C282Y mutation had higher transferrin saturation values; and men carrying HFE 63DD and 63HD genotypes had higher serum ferritin concentrations when compared to the wild genotype. Thirtyseven (72.5%) out of the 51 patients presented at least one HFE mutation and 11 were identified as homozygous for the mutation p.C282Y. One novel mutation (p.V256I) in the HFE gene was indentified and molecular modeling (free energy and structural analysis in silico) showed that p.V256I mutation did not reduce the affinity binding between HFE and β2-microglobulin. Sequencing in the HJV and HAMP genes revealed HJV p.E302K, HJV p.A310G, HJV p.G320V and HAMP p.R59G alterations. Sequencing in the TFR2 gene observed 3 polymorphisms (p.A75V, p.A617A e p.R752H); and sequencing in the SLC40A1 gene identified 6 polymorphisms (rs13008848, rs11568351, rs11568345, rs11568344, rs2304704 e rs11568346) and 1 p.G204S non-described mutation. The conclusions were: 1- for blood donors, the presence of HFE 282Y and...
Subject(s)
Humans , Male , Female , Middle Aged , Young Adult , Blood Donors/statistics & numerical data , Genetic Phenomena , Hemochromatosis/physiopathology , Hemochromatosis/genetics , Iron Overload/genetics , Analysis of Variance , Clinical Laboratory Techniques , Hematologic Diseases/genetics , Genetic Research , HematologyABSTRACT
En los últimos años, el estudio bioquímico y molecular de los diversos tipos de hemocromatosis ha llevado a la certeza de que el péptido hepcidina es el regulador central de la absorción de hierro. Este péptido que se sintetiza en el hígado ejerce su función a través de la degradación de la proteína ferroportina. La ferroportina es una bomba biológica de hierro situada en el epitelio intestinal y en la membrana de los macrófagos, su función es la de transportar hierro desde la célula intestinal al plasma y desde el macrófago al eritrón. En la hemocromatosis se produce un déficit físico o funcional de la hepcidina que conduce a un incremento de la ferroportina y, con esto, a una absorción de hierro excesiva. En situaciones de inflamación sucede lo contrario, se estimula la síntesis de hepcidina y se bloquea la entrada de hierro en el organismo y la síntesis de hemoglobina(AU)
In the last few years, biochemical and molecular study of the various types ofhemochromatosis have established that the hepcidin peptide is the central regulator of iron absorption. This peptide, which is synthesized in the liver, acts through ferro portin degradation. Ferroportin is an iron exporter situated in the intestinal epithelium and in the macrophage membrane whose function is to transport iron from the intestinal cell toplasma and from the macrophage to the erythron. In hemochromatosis, there is a physical or functional hepcidin deficit that in creases ferroportin, thus producing excessive iron absorption. The opposite occursin situation sof inflammation: hepcidin synthesisisstimulated while iron entry in to the organism and hemoglobin synthesis are blocked(AU)
Subject(s)
Humans , Hemochromatosis/physiopathology , Peptides/metabolism , Membrane Transport Proteins/metabolism , Intestinal Absorption/physiology , Iron, Dietary/metabolismABSTRACT
Fundamento y objetivo: Parece que un eslabón en la patogenia de la hemocromatosis hereditaria tipo 1 es la sobreexpresión de un transportador de cationes divalentes duodenal (DMT1) causante de la absorción del hierro2+ no hemínico. El objetivo del presente estudio ha sido valorar si el bloqueo competitivo de DMT1 mediante la administración de dosis altas de magnesio2+ por vía oral reduce la absorción de hierro en pacientes homocigotos para la mutación C282Y. Pacientes y método: Mediante un ensayo clínico cruzado se investigó la absorción de hierro mediante el test de absorción de bajas dosis de hierro en un grupo de 15 pacientes antes y después de ingerir durante 2 semanas una dosis de magnesio de 809,6 mg cada 8 h. Resultados: No se observaron efectos secundarios ni diferencias estadísticamente significativas entre la absorción de hierro antes y después del tratamiento experimental (14,7 µmol/l, intervalo de confianza [IC] del 95%, 9,8-19,6, frente a 14,9 µmol/l, IC del 95%, 8,5-21,4; p = 0,7). Conclusiones: El tratamiento con magnesio oral no reduce la absorción de hierro en los pacientes homocigotos C282Y. Dicho tratamiento no puede ser una alternativa terapéutica a las flebotomías
Background and objective: An essential step in the pathogenesis of hereditary hemochromatosis seems to be the increased expression of a duodenal divalent cation transporter (DMT1) responsible for absorption of non-heminic iron2+. The objective of the present study was to ascertain whether the competitive blockade of DMT1 by the administration of high doses of oral Mg2+ reduces iron absorption in patients homozygous for the C282Y mutation. Patients and method: Iron absorption was evaluated by a low dose iron absorption test in 15 patients before and after treatment with oral magnesium (809.6 mg every 8 hours) for two weeks. Results: We did not observe secondary effects or significant differences in iron absorption before or after magnesium treatment (14.7 µmol/L; 95% confidence interval [CI], 9.8-19.6 vs 14.9 µmol/L; 95% CI, 8.5-21.4, P = 0.7). Conclusions: Treatment with oral magnesium does not reduce iron absorption in homozygous C282Y patients. This treatment can not be used in these subjects
Subject(s)
Humans , Hemochromatosis/drug therapy , Magnesium/administration & dosage , Hemochromatosis/physiopathology , Cations, Divalent/analysis , Iron, Dietary/metabolism , Intestinal AbsorptionABSTRACT
Fundamento y objetivo: La hemocromatosis hereditaria (HH) presenta una importante variabilidad fenotípica y es una enfermedad en la que influyen muchos factores. Pacientes y método: Incluimos a 88 pacientes diagnosticados de HH, en los que se analizó los principales datos clínicos y analíticos y se valoró la influencia de 6 variables en la intensidad de la sobrecarga de hierro. Resultados: Un 38,6% (intervalo de confianza [IC] del 95%, 28,5-49,6) de los pacientes no mostró ninguno de los síntomas típicos de la enfermedad. Un 30,9% (IC del 95%, 21,7-41,7) presentaba alteraciones del metabolismo de la glucosa. Se detectó elevación de la sideremia en un 75,0% (IC del 95%, 64,4-83,3), del índice de saturación de la transferrina (IST) en un 95,4% (IC del 95%, 88,1-98,5) y de la ferritina sérica en un 93,2% (IC del 95%, 85,1-97,1) de los casos, respectivamente, además de objetivarse una elevación de la alaninoaminotransferasa y de la fosfatasa alcalina en un porcentaje apreciable de pacientes. La ferritina se elevó significativamente más en varones (1.329,4 [913,2] frente a 656,6 [644,5] ng/ml; p < 0,001), en mayores de 45 años (1.293,9 [1.006,9] frente a 868,9 [642,8] ng/ml; p = 0,023) y en no donantes de sangre (1205,2 [926,8] frente a 524,8 [365,9] ng/ml; p < 0,001). El IST fue del 81,9 (19,6%) en los homocigotos C282Y y del 65,7 (19,2%) en el resto de genotipos HFE (p = 0,002). No se detectó diferencias del IST respecto al sexo, la edad o la situación de donante de sangre. La sideremia fue significativamente mayor en los infectados por el virus de la hepatitis C (251,8 [24,4] frente a 182,8 [45,8] µg/dl; p = 0,001]). Conclusiones: Los pacientes de HH presentan una marcada variabilidad fenotípica, por lo que los síntomas sirven únicamente como orientación diagnóstica. Debe profundizarse en la relación entre la HH y el metabolismo de la glucosa. Los índices relacionados con el hierro pueden estar influidos por la edad, el sexo, el genotipo, la donación habitual de sangre, la ingesta de alcohol y la infección por el virus de la hepatitis C
Background and objective: Hereditary hemochromatosis (HH) displays an important phenotypic variability and is a disease influenced by many factors. Patients and method: We included 88 patients with HH. Main clinical and laboratory data were analyzed, and the influence of 6 variables on intensity of iron overload was evaluated. Results: In 38.6% (95% confidence interval [CI], 28.5-49.6%) patients, none of the typical symptoms of the disease was observed. 30,9% (95% CI, 21.7-41.7%) showed abnormalities of the glucose metabolism. We detected an increase in sideremia in 75.0% patients (CI 95%, 64.4-83.3%), transferrin saturation index (TSI) in 95.4% (CI 95%, 88.1-98.5%) and ferritin in 93.2% (CI 95%, 85.1-97.1%) of patients. In addition, we observed increased values of GPT and alkaline phosphatase in an appreciable percentage of patients. Ferritin was significantly higher in men (1329.4 [913.2] ng/ml vs 656.6 [644.5] ng/ml; p < 0.001), and in those older than 45 years (1293.9 [1006.9] ng/ml vs 868.9 [642.8] ng/ml; p = 0.023] and in not blood donors (1205.2 [926.8] vs 524.8 [365.9] ng/ml; p < 0.001). TSI was 81.9% (19.6) in C282Y homozygotes and 65.7% (19.2) in the rest of HFE genotypes (p = 0.002). Differences of TSI with regard to sex, age or status of blood donor were not detected. Sideremia was significantly higher in patients infected by virus C (251.8 [24.4] µg/dl vs 182.8 [45.8] µg/dl; p = 0.001). Conclusions: HH patients have a noticeable phenotypic variability, and for that reason clinical symptoms are only orientative for the diagnosis. The relationship between HH and glucose metabolism should be investigated further. Iron parameters can be influenced by age, sex, HFE genotype, blood donation, alcohol intake and hepatitis C virus infection
Subject(s)
Male , Female , Adult , Aged , Middle Aged , Humans , Iron Overload/physiopathology , Hemochromatosis/physiopathology , Phenotype , Spain/epidemiology , Transferrin/analysis , Glucose Metabolism Disorders/epidemiology , Hepatitis C, Chronic/complications , Ferritins/analysisABSTRACT
No disponible
Subject(s)
Humans , Hemochromatosis/genetics , Hemochromatosis/metabolism , Hemochromatosis/physiopathology , Cation Transport Proteins/genetics , Iron/metabolism , Iron Overload/genetics , Iron Overload/physiopathology , Receptors, Transferrin/geneticsABSTRACT
La hemocromatosis es un trastorno hereditario del metabolismo del hierro muy común en América y norte de Europa, donde afecta del 0,3 al 0,8 por ciento de la población. Se caracteriza por un depósito progresivo de hierro en las células parenquimatosas del hígado, el corazón y otros órganos; finalmente, conduce a su alteración. Trousseau en el siglo XIX encontró una asociación entre cirrosis, diabetes y pigmentación. Recklinghausen, en 1989, identificó el pigmento como hierro y denominó a esta enfermedad hemocromatosis. Consideró que el origen del hierro era la sangre. En 1935, Sheldon revisó 311 casos previamente publicados de hemocromatosis y concluyó que la enfermedad era causada por una alteración en el metabolismo del hierro. Recientes desarrollos en medicina molecular han permitido la localización, a partir de estudios del HLA, del déficit genético de la hemocromatosis junto a los genes HLA en el brazo corto del cromosoma 6 4,5. Sin embargo, el gen no fue identificado hasta 1996 gracias a importantes esfuerzos en clonación posicional. A partir de ese momento, se establece un criterio más preciso para realizar el cribado y el diagnóstico de esta enfermedad (AU)
Subject(s)
Adolescent , Female , Male , Humans , Hemochromatosis/diagnosis , Hemochromatosis/therapy , Hemochromatosis/etiology , Iron/metabolism , HLA-A Antigens/genetics , Ferritins/administration & dosage , Ferritins/therapeutic use , Hemochromatosis/genetics , Hemochromatosis/physiopathology , Iron Overload/etiology , Receptors, Transferrin , Genetic TestingABSTRACT
Hemocromatose hereditária é o termo usado para identificar uma doença ligada ao complexo maior de histocompatibilidade humana, de herança genética, onde há um inapropriado aumento da absorção intestinal de ferro. Cirrose hepática, diabetes, artrite e cardiopatia são achados frequentes em pacientes com a doença estabelecida. Os autores relatam caso de paciente com essa enfermidade e fazem uma revisão na literatura especializada acerca de sua fisiopatologia, métodos diagnósticos e terapêutica