ABSTRACT
La hemocromatosis es una enfermedad caracterizada por el excesivo depósito de hierro en múltiples órganos, entre ellos hígado, páncreas, piel y corazón. La infiltración de este último es un importante factor en morbilidad y mortalidad. Presentamos un caso de un paciente pediátrico con insuficiencia cardíaca terminal que ameritó trasplante cardíaco, que resultó sin complicaciones. Posterior a la cirugía, mostró mejoría bioquímica y clínica, lo que influyó positivamente en su calidad de vida y prolongó su supervivencia.
Hemochromatosis is a disease characterized by excess iron stores in multiple organs, including the liver, pancreas, skin, and heart. The infiltration of the heart is an important factor in morbidity and mortality. Here we describe the case of a pediatric patient with end-stage heart failure who required a heart transplantation, with no complications. After the surgery, she showed biochemical and clinical improvement, with a positive impact on her quality of life and a prolonged survival.
Subject(s)
Humans , Female , Child , Heart Transplantation , Iron Overload/complications , Hemochromatosis/complications , Hemochromatosis/diagnosis , Quality of Life , LiverABSTRACT
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
Abstract Hemochromatosis is currently characterized by the iron overload caused by hepcidin deficiency. Large advances in the knowledge on the hemochromatosis pathophysiology have occurred due to a better understanding of the protein of the iron metabolism, the genetic basis of hemochromatosis and of other iron overload diseases or conditions which can lead to this phenotype. In the present review, the main aims are to show updates on hemochromatosis and to report a practical set of therapeutic recommendations for the human factors engineering protein (HFE) hemochromatosis for the p.Cys282Tyr (C282Y/C282Y) homozygous genotype, elaborated by the Haemochromatosis International Taskforce.
Subject(s)
Humans , Male , Female , Iron Metabolism Disorders , Hemochromatosis/diagnosis , Hemochromatosis/therapy , Phlebotomy , Iron Overload , Hepcidins/deficiency , Hemochromatosis ProteinABSTRACT
La hemocromatosis hereditaria es una enfermedad genética de difícil diagnóstico, en estadios iniciales, ocasionada por alteraciones en el metabolismo del hierro; que conllevan a su depósito en diversos tejidos y como resultado una gran morbilidad en los pacientes afectados. A través de este trabajo se realizó la presentación del primer caso diagnosticado por gastroenterólogos, en el Hospital Faustino Pérez de Matanzas. El paciente debutó con síntomas relacionados con la esfera endocrina como: impotencia, pérdida de la líbido y de la eyaculación. Después de efectuar los estudios correspondientes se concluyó como un hipogonadismo hipogonadotrópico post puberal, por presentar elevación de las enzimas hepáticas. Fue remitido a consulta de Hepatología donde se completó su estudio, confirmándose el diagnóstico de hemocromatosis hereditaria tipo I, a través de biopsia hepática y estudios genéticos (AU).
Hereditary hemocrhomatosis is a genetic disease of difficult diagnosis in its early stages, caused by alterations in the iron metabolism; it leads to iron storage in several tissues and consequently to a great morbidity in affected patients. In this work, we presented the first case diagnosed by gastroenterologists in the Hospital Faustino Pérez, of Matanzas. The patient began with symptoms related with the endocrine sphere like impotence, and lost of libido and ejaculation. After finishing the correspondent studies, we arrived to the conclusion of post-pubertal hypogonadotropic hypogonadism: the patient presented hepatic enzymes elevation. He was referred to Hepatology consultation where the study was finished, confirming the diagnosis of Type I hereditary hemocrhomatosis through biopsy and genetic studies (AU).
Subject(s)
Humans , Male , Young Adult , Iron Metabolism Disorders/complications , Iron Metabolism Disorders/genetics , Hemochromatosis/congenital , Hemochromatosis/diagnosis , Hemochromatosis/genetics , Case Reports , Genetic Diseases, Inborn/diagnosisABSTRACT
La enfermedad hepática gestacional aloinmune, previamente conocida como hemocromatosis neonatal, se caracteriza por enfermedad hepática grave que se inicia en el período neonatal, asociada al acúmulo intra- y extrahepático de hierro. Se postula un potencial origen aloinmune, lo que ha abierto posibilidades en el tratamiento y en la prevención durante los embarazos de riesgo y ha cambiado el pronóstico de esta patología. Exponemos el caso de una recién nacida que presentó falla hepática precoz, con características clínicas y analíticas compatibles con enfermedad hepática gestacional aloinmune. Se realizó una exanguinotransfusión y se administró tratamiento con gammaglobulinas, con buena evolución posterior de la paciente.
Gestational alloimmune liver disease, previously known as neonatal hemochromatosis, is characterized by severe liver disease in neonatal period, associated with intra and extrahepatic iron accumulation. It is postulated an alloimmune origin, which has opened new opportunities in the treatment and prevention during risk pregnancies, changing the prognosis of this pathology. We report the case of a newborn that presents early liver failure, with clinical and analytical features compatible with gestational alloimmune liver disease. Exchange transfusion was made and gamma globulins were given, with good clinical evolution.
Subject(s)
Humans , Female , Infant, Newborn , Hemochromatosis/diagnosisABSTRACT
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
Este é um relato de uma paciente que teve diagnóstico prévio de artrite reumatoide, não erosiva, fator reumatoide negativo, que apesar da terapêutica instituída apresentava piora progressiva do quadro articular e do estado geral. Após extensa investigação, apresentou diagnóstico de hemocromatose. Sintomas articulares são manifestações frequentes na hemocromatose. A artropatia da hemocromatose pode assemelhar-se a artropatias inflamatórias imitando a AR, particularmente nos sítios mais comuns, como 2ª e 3ª metacarpofalangeanas. Radiologicamente são observadas diminuição do espaço articular, esclerose subcondral, formação de cistos e condrocalcinose. O tratamento com drogas modificadoras de doença para artrite reumatoide tende a piorar o quadro clínico, uma vez que o fígado é o principal sítio de depósito de ferro na hemocromatose e essas medicações são sabidamente hepatotóxicas. O tratamento com flebotomia para hemocromatose é aparentemente ineficaz na reversão das manifestações articulares, sendo necessária a associação com medicações quelantes de ferro. Devido à dificuldade aparente de diferenciação entre as duas patologias, faz-se necessária uma triagem no perfil do ferro em pacientes com diagnóstico de artrite reumatoide com evolução atípica.
This is a report of a patient who had a previous diagnosis of rheumatoid arthritis, nonerosive, rheumatoid factor negative, that despite the therapeutic approach presented progressive worsening of the articular and general condition. After extensive research, she had a diagnosis of hemochromatosis. Joint symptoms are common manifestations in hemochromatosis. The arthropathy of hemochromatosis may resemble inflammatory arthropathy mimicking RA, particularly in the most common sites as 2nd and 3rd metacarpophalangeal. Radiologically are observed decreased joint space, subchondral sclerosis, cyst formation and chondrocalcinosis. Treatment with disease modifying drugs for rheumatoid arthritis tend to worsen the clinical picture, since the liver is the major site of deposition of iron in hemochromatosis and these medications are known to be hepatotoxic. Phlebotomy treatment for hemochromatosis is apparently ineffective in reversing the articular manifestations, which requires the association with iron chelating drugs. Due to the apparent difficulty in differentiating between the two diseases, a screening profile of iron in patients with rheumatoid arthritis with atypical progression is necessary.
Subject(s)
Female , Humans , Middle Aged , Arthritis, Rheumatoid/diagnosis , Hemochromatosis/diagnosis , Diagnosis, DifferentialSubject(s)
Humans , Male , Middle Aged , Hyperpigmentation , Hemochromatosis/complications , Hemochromatosis/diagnosis , Fatal Outcome , Ferritins/blood , Hemochromatosis/therapy , Iron/blood , PhlebotomyABSTRACT
El modelo clásico de la hemocromatosis neonatal contemplaba la analogía con la hemocromatosis hereditaria. El tratamiento médico se basaba en un cóctel quelante/antioxidante. La hipótesis actual de un origen aloinmunitario del proceso, en el que la madre gestante monta una respuesta destructiva de tipo IgG contra los hepatocitos fetales, ha ofrecido una mejor explicación fsiopatológica y permite enfocar el tratamiento en el aspecto inmunológico con excelentes resultados, incluso previniendo la enfermedad en embarazos posteriores. Este cambio de paradigma repercute profundamente en el diagnóstico, pronóstico y tratamiento de la enfermedad, que debería denominarse "hepatitis fetal aloinmunitaria".
The classical model of neonatal hemochromatosis was based on the analogy with hereditary hemochromatosis. Medical treatment consisted on the antioxidant-chelator cocktail. The new hypothesis of an alloimmune origin of the process by which the pregnant woman mounts an IgG-based destructive response against fetal hepatocytes offers a pathogenic explanation, allowing treatment to be focused on the immunological aspects, with excellent results, and opens the possibility of preventive treatment in future pregnancies. This new paradigm produces a deep impact in diagnosis, prognosis and treatment of the disease, that should be called "fetal alloimmune hepatitis".
Subject(s)
Humans , Infant, Newborn , Hemochromatosis/immunology , Fetal Diseases/immunology , Hemochromatosis/diagnosis , Hemochromatosis/drug therapy , Hemochromatosis/etiologyABSTRACT
O diagnóstico da hemocromatose hereditária (HH) em fase pré-cirrótica é um desafio, uma vez que os pacientes não apresentam sintomas ou sinais da doença. Relata-se caso de mulher de 62 anos que, submetida à colecistectomia videolaparoscópica para tratamento de coletilíase, apresentou fígado de aspecto alterado, sendo realizada biópsia hepática com agulha. O exame histológico do fígado pelo método de Perls mostrou grande quantidade de pigmento férrico, suspeitando-se de HH. Realizado estudo do metabolismo do ferro e teste genético para HH, confirmou-se a doença. A biópsia hepática, portanto, é de fundamental importância no diagnóstico da HH, devendo ser realizada toda vez que o cirurgião, por ocasião de cirurgia abdominal, observar fígado de aspecto não habitual.
The diagnosis of pre-cirrhotic hereditary hemochromatosis (HH) is difficult because there are no signs and symptoms in HH patients. We described a case of a 62-years old woman with cholelithiasis that was carried out a videolaparoscopic cholecystectomy. At surgery, the liver had been a altered aspect and liver needle biopsy was carried out. The histopathologic study by Persl method showed a great accumulation of iron pigment in hepatic tissue. The study of iron metabolism and genetic test for HH was released and the diagnosis of HH was confirmed. The liver biopsy is a gold standard procedure for diagnosis of HH and must be released when, at abdominal surgery, the surgeon to observe a liver with altered aspect.
Subject(s)
Humans , Female , Middle Aged , Biopsy , Hemochromatosis , Liver , Hemochromatosis/diagnosis , Hemochromatosis/pathology , Genetic Diseases, Inborn/diagnosisABSTRACT
Iron accumulation in parenchymal cells results in toxic damage and cell death which can determine a functional organ failure. The prototypical disease is hereditary hemochromatosis (HH). HH has been associated to mutations affecting any of the proteins that regulate iron metabolism. The most common cause of HH is a mutation in the HFE gene [C282Y]. Mutations in the gene for the hormone hepcidin and any of other eight genes that regulate iron biology, including the transferrin receptor 2 (TfR2), hemojuvelin (HJV) and ferroportin (FPN), also cause iron overload and hemochromatosis. Although information is limited, HFE-associated to HH is uncommon in Chile. Evaluation of iron overload in clinical practice should include consideration of co-factors such as alcohol consumption, the presence of virus infection hepatitis C virus and nonalcoholic steatohepatitis, which independently can contribute to iron accumulation. While genetic testing is useful, analysis of liver histology and imaging evaluation of iron overload by MRI are important tools for clinical evaluation. This article reviews current concepts on the clinical diagnosis and management of hepatic iron overload.
La acumulación de hierro en las células parenquimatosas determina la ocurrencia de daño tóxico y muerte celular, lo que puede producir una insuficiencia funcional. La enfermedad prototípica es la hemocromatosis hereditaria (HH). La HH se ha asociado a mutaciones que afectan a cualquiera de las proteínas que regulan el metabolismo del hierro. La causa más común de HH es una mutación en el gen HFE [C282Y]. Mutaciones en el gen de la hormona hepcidina (HAMP) y cualquiera de los 8 genes que regulan su biología, incluyendo el receptor de transferrina 2 (TfR2), hemojuvelina (HJV) y ferroportina(FPN), también causan sobrecarga de hierro y hemocromatosis. Aunque la información es limitada, la HH asociada a HFE es infrecuente en nuestro medio. La evaluación de la sobrecarga de hierro en la práctica clínica debe contemplar la evaluación de otros factores tales como el consumo de alcohol, la presencia de infección por el virus de la hepatitis por virus C y de esteatohepatitis no alcohólica. Si bien el test genético es de utilidad, los análisis de la histología hepática y la evaluación imagenológica de la sobrecarga de hierro mediante resonancia magnética son útiles para la evaluación clínica de la sobrecarga de hierro. El presente artículo revisa conceptos actuales sobre el manejo clínico de la sobrecarga de hierro hepática.
Subject(s)
Humans , Hemochromatosis/complications , Hemochromatosis/diagnosis , Hemochromatosis/therapy , Liver Diseases/complications , Phlebotomy , Hemochromatosis/classification , Hemochromatosis/etiology , Antimicrobial Cationic PeptidesABSTRACT
Portadores de talassemia major (TM) permanecem assintomáticos e com funções ventriculares preservadas por longo tempo, porém, duas condições básicas podem ser responsáveis pelo comprometimento da função cardíaca nesse indivíduos, a anemia e a hemocromatose. Recentes avanços na ecocardiografia possibilitaram a utilização dessa técnica para a identificação precoce de disfunção ventricular secundária à hemocromatose. Além disso, esse exame constitui instrumento valioso para o acompanhamento evolutivo de pacientes, permitindo comparações de variáveis estruturais e funcionais cardíacas em diferentes momentos.
Subject(s)
Humans , Echocardiography, Doppler/methods , Echocardiography, Doppler , Hemochromatosis/complications , Hemochromatosis/diagnosis , Thalassemia/complications , Thalassemia/diagnosis , Ventricular RemodelingABSTRACT
A Hemocromatose Hereditária (HH) é a desordem hereditária mais comum em caucasianos. Mais de 90% dos casos de HH resultam da simples substituição do aminoácido Cisteína pela Tirosina no gene HFE. Essa mutação causa uma doença recessiva que resulta no acúmulo tissular de ferro. O mecanismo através do qual o HFE influencia a homeostase do ferro nas células e no corpo permanece obscuro. A doença é subdiagnosticada na população em geral devido à inespecificidade de sua apresentação clínica. O prognóstico envolve a detecção precoce da doença e a terapêutica adequada utilizando a flebotomia em fase oportuna. Essa revisão descreve os conceitos atuais a respeito das manifestações clínicas, fisiopatologia, prognóstico e tratamento da Hemocromatose Hereditária relacionada ao gene HFE.
Hereditary hemochromatosis (HH) is the most common inherited disorder in caucasians. Over 90% of the cases of HH result from a single mutation of a Cys to Tyr in the HFE gene. This mutation causes a recessive disease resulting in iron acumulation in selected tissues. The mechanism by which HFE influences iron homeostasis in cells and in the body remains elusive. The disease is underdiagnosed in general population due to inespecific clinical manifestations. Prognosis is related to early diagnostic and correct treatment using pheblotomy. This review describe the current concepts concerning the clinical features, pathophisiology, prognosis and treatment of HFE-related hemochromatosis hereditary.
Subject(s)
Humans , Iron Overload/genetics , Hemochromatosis Protein/genetics , Hemochromatosis/diagnosis , Hemochromatosis/genetics , Hemochromatosis/therapy , Mutation/genetics , Brazil , Phlebotomy/instrumentation , Deferoxamine/therapeutic use , White People/geneticsSubject(s)
Female , Humans , Middle Aged , Cardiomyopathy, Restrictive/pathology , Multiple Myeloma/diagnosis , Amyloidosis/diagnosis , Amyloidosis/etiology , Cardiomyopathies/diagnosis , Diagnosis, Differential , Fatal Outcome , Fabry Disease/diagnosis , Fabry Disease/etiology , Hemochromatosis/diagnosis , Hemochromatosis/etiology , Multiple Myeloma/complications , Multiple Myeloma/pathology , Proteinuria/etiology , Proteinuria/urine , Renal Insufficiency , Sarcoidosis/diagnosis , Sarcoidosis/etiologyABSTRACT
La hemocromatosis neonatal es una entidad clínico patológicaque presenta fallo hepático grave, se inicia in útero, asociada a siderosis intrahepática y extrahepática, que respeta el sistema reticulo endotelial.Su causa se desconoce pero se debería a un manejo anormal del hierro fetoplacentario con enfermedad hepática perinatal, relación genética familiar o sería consecuencia de una enfermedad gestacional aloinmunitaria. Es un síndrome con características comunes más que una simple entidad patológica, con transmisión materna y alta recurrencia en la misma progenie. La muerte se produceen los primeros días o semanas de vida por fallomultiorgánico. Presentamos dos recién nacidos con hemocromatosis neonatal. El primero falleció por fallo multiorgánico y el segundo permitió el trasplante hepático. Desde 1993, se emplea un cocktail antioxidantequelantedel hierro, junto al tratamiento de soporteestándar del fallo hepático, pero su uso es polémico. En 2002, una comunicación preliminar sugiere que el tratamiento con inmunoglobulinas endovenosas en la segunda mitad de la gestación, en mujeres con el antecedente de un hijo con hemocromatosis neonatal probada, previene las formas recurrentes letales de la enfermedad. Este trastorno se debe sospechar en todo fallo hepático grave al nacer, acompañado de valores séricos de ferritina elevados; pero debe confirmarse por un aumento de los depósitos hepáticos de hierro y siderosis extrahepática demostrables por resonancia magnética nuclear, en la biopsia de glándulas salivales o en la autopsia. La hemocromatosis neonatal es la indicación específicamás frecuente de trasplante hepático en los primeros 3 meses de vida, que parecería ser el tratamiento de elección por considerar desde el momentoque el soporte médico, incluida la terapia antioxidante-quelante del hierro, sea inefectivo, antes de que surjan complicaciones neurológicas irreversibles
Neonatal hemochromatosis is a rare clinical pathologic entity, defined by severe neonatal liver failure of intrauterine onset associated with intra-and extra hepatic siderosis that spares reticuloendothelial system. It is the most frequently recognized cause of liver failure in neonates. The cause is unknown but it may develop secondary to abnormal fetoplacental iron handling or perinatal liver disease or be familial or as a consequence of gestational alloimmune disease. Its a syndrome with a common feature rather than a single pathologic entity, with maternal transmission and a high recurrence in the sibship. Death from multisystem organ failure usually occurs in the first few days or weeks of life. We report two newborn with neonatal hemochromatosis. The first died for multiorgan failure, despite aggressive support. The second underwent to liver transplantation. Since 1993, an antioxidant-chelator cocktail has been used in addition to standard supportive care, but this remains controversial. By 2002, a preliminary report suggested that treatment with weekly intravenous immunoglobulin during the later half of pregnancy, for woman whose most recent gestation was affected with proven NH. The diagnosis is suspected in the presence of severely impaired hepatic synthetic function accompanied by high serum ferritin levels, but is confirmed only by demonstration of increased hepatic iron stores, and extra-hepatic siderosis shown by autopsy or in vivo, which can be achieved by biopsy of the minor salivary glands or magnetic resonance imaging. Neonatal hemochromatosis is the most common specific indication for liver transplantation in the first three months of life and appears to be the treatment of choice, and must as well be considered as soon as it becomes apparent that medical support, which should include chelation-antioxidant treatment, is ineffective, before irreversible neurological complications appear.