Trasplante cardíaco por hemocromatosis. Caso pediátrico / Cardiac transplantation due to hemochromatosis. A pediatric case report

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.

Sobrecarga de hierro y enfermedad hepática: aspectos clínicos y terapéuticos / Iron overload and liver disease: clinical and therapeutic issues

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.

Avaliação da função diastólica em portadores de talassemia major / Diastolic function in patients with thalassemia major

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.

Complete Hematopoietic Recovery after Continuous Iron Chelation Therapy in a Patient with Severe Aplastic Anemia with Secondary Hemochromatosis

A 16-yr-old male patient with hemochromatosis due to multiple packed red blood cell transfusions was referred to our emergency center for the treatment of severe aplastic anemia and dyspnea. He was diagnosed with aplastic anemia at 11-yr of age. He had received continuous transfusions because an HLA-matched marrow donor was unavailable. Following a continuous, approximately 5-yr transfusion, he was noted to develop hemochromatosis. He had a dilated cardiomyopathy and required diuretics and digitalis, multiple endocrine and liver dysfunction, generalized bleeding, and skin pigmentation. A total volume of red blood cell transfusion before deferoxamine therapy was about 96,000 mL. He received a regular iron chelation therapy (continuous intravenous infusion of deferoxamine, 50 mg/kg/day for 5 days q 3-4 weeks) for approximately seven years after the onset of multiple organ failures. His cytopenia and organ dysfunctions began to be gradually recovered since about 2002, following a 4-yr deferoxamine treatment. He showed completely normal ranges of peripheral blood cell counts, heart size, and liver function two years ago. He has not received any transfusions for the last four years. This finding suggests that a continuous deferoxamine infusion may play a role in the immune regulation in addition to iron chelation effect.

Aparición de porfiria cutánea tarda durante el tratamiento con peg-interferón más ribavirina en un paciente con hepatitis C crónica con viremia indetectable / Development of porphyria cutanea tarda in a chronic hepatitis C patient with indetectable viremia under treatment with peg-interferon plus ribavirin

La porfiria cutánea tarda (PCT) es considerada una manifestación extrahepática de la infección por el virusde la hepatitis C (HCV). La frecuencia de esta asociación es variable y no es claro el mecanismo por el cual el virus la desencadena. Se presenta un hombre de 47 años con hepatitis C, genotipo-1b, que durante el tratamiento con peg-interferón alfa-2b más ribavirinasin viremia detectable en las semanas 12, 24 y 48, en la semana 44 consulta por presentar lesiones dermatológicasfotosensibles. Con el diagnóstico presuntivo de PCT se realizó biopsia cutánea y el dosaje de porfirinasurinarias fue 4185 ug/24hs (vn: < 250). El análisis cromatográfico reveló el típico patrón de PCT, confirmando el diagnóstico. El gen HFE de la hemocromatosis mostró mutaciones de carácter heterocigoto (H63D y C282Y), asociación frecuente en los pacientescon sobrecarga de hierro y PCT. El tratamiento antiviral de la infección por HCV puede mejorar las manifestacionesde la PCT. La ocurrencia de novo de éstafue reportada recientemente durante el tratamiento de la hepatitis C crónica con interferón y ribavirina pero no hay casos relatados de aparición tardía de PCT enpacientes HCV con viremia no detectable. La presencia de la mutación del gen HFE y la posibilidad de unaumento de oferta de hierro por la acción hemolítica de la ribavirina podrían explicar un exceso de hierrocapaz de desencadenar la crisis de PCT. Tampoco sonconcluyentes los estudios con respecto al aumento o no de la concentración de hierro en hígado en pacientes con anemia que reciben ribavirina.

Porphyria cutanea tarda (PCT) is considered an extra-hepatic manifestation of HCV infection. The frequency of this association varies according to different authors and the mechanism by which the virus can trigger this disease is not yet clear. We present a 47-year-old-man with chronic hepatitis C genotype 1b who, during the treatment with peg-interferón alfa 2b plus ribavirina, with no detectable viremia at weeks 12th, 24th, and 48th, developed dermatological photosensitive lesions at week 44th. With a presumptive diagnosis of PCT a cutaneous/skin biopsy was performed as well as a porphyrin dosage with urine porphyirins of 4185 microg/24 hs (nv<250). The chromatographic analysis revealed the typical PCT pattern thus confirming the diagnosis. The hemochromatosis HFE gen evaluation showed heterozigotus character mutations (H63D and C282Y) a frequent association in patients with iron overload and PCT. The antiviral treatment of the HCV infection can improve the clinical-humoral manifestations of PCT. The novo occurrence of PCT was recently reported during chronic hepatitis C treatment with interferón and ribavirin, but no cases of late appearance of PCT in patients with no detectable viremia were reported. The mutation of the gen HFE in our patient and the hemolysis caused by ribavirin can be related to the development of the disease, but the iron overload because of ribavirin use is also controversial. This is another example of the complexity of this association.

Curaçao patients with coronary artery disease have a higher prevalence of the HFE C282Y mutation

Epidemiological studies indicate a positive relation between iron status and coronary artery disease (CAD) risk The HFE C282Y allele is associated with increased iron status and higher CAD risk. We investigated whether HFE C282Ymight be a CAD risk factor in Curaçao in a case-control study design. The patient group comprised 42 men and 10 women. Fifty-four men and 30 women without history of CAD served as age and gender matched controls. HFE C282Y genotypes were established using sequence-specific priming polymerase chain reaction. None of the investigated subjects were homozygous for HFE C282Y, whereas 5/52 (9.6) CAD patients and 1/84 controls (1.2) were heterozygous for HFE C282Y (p = 0.03). The HFE C282Y mutation was 8.8 fold (95 CI 1.001, 77.8; p = 0.049) more prevalent in CAD patients than in controls. The HFE C282Y allele frequency in Curaçao is higher than that of African populations, but comparable with that of Jamaica. We conclude that Curaçao CAD patients have somewhat higher frequency of HFE C282Y heterozygosity than controls, and that the HFE C282Y allele frequency in the Curaçao population is higher than might be expected in persons of African descent. The consequences of HFE C282Y heterozygosity as CAD risk factor are as yet uncertain, since there is no proof that iron lowering reduces CAD risk

Non HFE-related hemochromatosis; a case report from Iran

Hemochromatosis, especially with cardiac and liver problem, is rare in Iran. We report a young female with pulmonary hypertension and abnormal liver function tests due to non HFE- related hemochromatosis

Hemocromatose hereditária / Hereditary haemochromatosis

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

Neuroimagem na degeneraçäo hepatocerebral induzida por hemocromatose / Neuroimage findings in hepatocerebral degeneration induced by hemochromatosis

Säo demonstradas alteraçöes transitórias bipalidais caracterizadas por hiperintensidade na sequência T1 da ressonância nuclear magnética, que ocorreram em um paciente com degeneraçäo hepatocerebral adquirida provocada por hemocromatose. Em funçäo de acrescentar-se a este sinal a visibilizaçäo de imagem de hiperintensidade bitalâmica na sequência T2, discute-se a hipótese destes sinais serem unicamente secundários â degeneraçäo hepatocerebral ou, ainda, se teriam sido também originados pela própria hemocromatose.

Abscesos hepatoesplénicos múltiples por yersina enterocolítica en un paciente con hemocromatosis / Multiple hepato-splenic abscesses caused by yersinia enterocolitica in a patient with hemochromatosis

Yersinia enterocolitica is a gram-negative bacillus that thrives in conditions associated with iron overload. We decribe an unusual case of a diabetic patient with a previously unrecognized hemochromatosis presenting with Y. enterocolitica septicemia. He was admitted because of a 10 day history of abdominal pain, fever and jaundice. Blood cultures grew Y. enterocolitica. The abdomen CT scan showed multiple liver and splenic abscesses. Antibiotic treatment with ciprofloxacin (2 months) resulted in a good clinical response. Serum iron studies showed iron overload. Liver biopsy revealed moderate fibrosis and early cirrhosis with large amounts of hemosiderin granules deposited in hepatocytes and bile duct epithelium. This report reviews the literature and highlighsts that iron overload must be ruled out in Yersinia septicemia patients

Genetic hemochromatosis presenting as asymptomatic hepatomegaly.

A case of genetic hemochromatosis presented with asymptomatic hepatomegaly. The diagnosis was based on elevated serum iron, serum ferritin and transferrin saturation, a characteristic picture on magnetic resonance imaging, and liver biopsy showing cirrhosis with excessive iron deposits in the liver parenchyma. The extreme rarity of this disease in our country is perhaps determined by hereditary factors.

Pituitary and testicular involvement in primary haemochromatosis. A case report.

A case of primary hemochromatosis with hypogonadotropic hypogonadism and decreased Leydig cell reserve is reported.

Idiopathic hemochromatosis in a young man presenting with palpitations

Un hombre de 32 años presentó con queja de palpitaciones y nivels elevados de hierro sérico. Evaluación posterior reveló elevación de la ferritina en suero, y una biopsia de hígado confirmó el diagnóstico de hemocromatosis. La evaluación cardiovascular fue normal excepto por bradicardia sinusal alternando con taquicardia sinusal en un Holter de 24 horas. El paciente se comenzó en tratamiento con flebotomías semanales y la familia se esta evaluando para detectar tempranamente cualquier otro caso. Las manifestaciones, evaluación diagnóstica e importancia del diagnóstico temprano son enfatizadas

Neonatal hemochromatosis: report of an autopsy case

A case of neonatal hemochromatosis in a 3-hour-old male is described. He presented with hypotonia, mild jaundice, and respiratory difficulty immediately after birth. He had no evidence of congenital infection, immune-related hemolysis or exogenous iron uptake. Postmortem examination revealed abnormal facial features. The organs were of normal weight for his age except a small liver and lungs, and a large spleen. The most prominent changes were in the liver and pancreas. The liver was coarsely nodular and fibrotic. The lobular architecture was totally distorted by innumerable multinucleated giant cells, loss or collapse of the hepatocytes, and diffuse fibrosis. A large amount of hemosiderin was seen in the liver, pancreatic acini and thyroid follicular cells. Scanty amount of hemosiderin was also found in the myocardial fibers and renal tubular cells. The pancreas showed hyperplasia and hypertrophy of the islets. The spleen showed severe congestion and a moderate extramedullary hemopoiesis but no deposits of hemosiderin. This patient had three siblings died in neonatal period, one of which had clinical features of neonatal hemochromatosis.