RESUMEN
Iron-refractory iron-deficiency anemia (IRIDA) is a rare autosomal-recessive disorder characterized by hypochromic microcytic anemia, low transferrin saturation, and inappropriate high levels of the iron hormone hepcidin. The disease is caused by variants in the transmembrane protease serine 6 (TMPRSS6) gene that encodes the type II serine protease matriptase-2, a negative regulator of hepcidin transcription. Sequencing analysis of the TMPRSS6 gene in 21 new IRIDA patients from 16 families with different ethnic origin reveal 17 novel mutations, including the most frequent mutation in Southern Italy (p.W590R). Eight missense mutations were analyzed in vitro. All but the p.T287N variant impair matriptase-2 autoproteotylic activation, decrease the ability to cleave membrane HJV and inhibit the HJV-dependent hepcidin activation. Genotype-phenotype studies in IRIDA patients have been so far limited due to the relatively low number of described patients. Our genotype-phenotype correlation analysis demonstrates that patients carrying two nonsense mutations present a more severe anemia and microcytosis and higher hepcidin levels than the other patients. We confirm that TMPRSS6 mutations are spread along the gene and that mechanistically they fully or partially abrogate hepcidin inhibition. Genotyping IRIDA patients help in predicting IRIDA severity and may be useful for predicting response to iron treatment.
Asunto(s)
Anemia Ferropénica/diagnóstico , Anemia Ferropénica/genética , Estudios de Asociación Genética , Variación Genética , Genotipo , Proteínas de la Membrana/genética , Fenotipo , Serina Endopeptidasas/genética , Adolescente , Adulto , Anemia Ferropénica/terapia , Niño , Preescolar , Femenino , Frecuencia de los Genes , Orden Génico , Sitios Genéticos , Humanos , Lactante , Masculino , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Mutación , Serina Endopeptidasas/química , Serina Endopeptidasas/metabolismo , Adulto JovenRESUMEN
Management of haemophilia carrier women during labour and postpartum is yet to be standardized. Pregnancy was accompanied by a marked rise in factor VIII levels compared with only a small rise in factor IX levels. After delivery, a carrier's factor level drops down to prepregnancy levels, which increases the chance of postpartum haemorrhage. Availability of management guideline and care provided in a multidisciplinary approach can help to minimize bleeding complications in carriers of haemophilia and their newborns.
Asunto(s)
Hemofilia A/complicaciones , Hemofilia B/complicaciones , Hemorragia Posparto/etiología , Complicaciones Hematológicas del Embarazo/etiología , Femenino , Hemofilia A/sangre , Hemofilia A/genética , Hemofilia B/sangre , Hemofilia B/genética , Hemostasis , Heterocigoto , Humanos , Recién Nacido , Parto , Hemorragia Posparto/sangre , Hemorragia Posparto/genética , Periodo Posparto , Embarazo , Complicaciones Hematológicas del Embarazo/sangre , Complicaciones Hematológicas del Embarazo/genéticaRESUMEN
Objetivo. evaluar los casos de transfusión intravascular intrauterina por anemia fetal realizados en la Unidad de Medicina Fetal del Hospital Universitario Materno Infantil de Canarias. Material y método. estudio descriptivo y prospectivo de los casos diagnosticados de anemia fetal y a los que posteriormente se sometió a transfusión intravascular intrauterina en el período comprendido entre mayo de 2007 y junio de 2009. Resultados. durante ese período se diagnosticaron 7 casos de anemia fetal: 4 de anemia fetal inmune y 3 no inmune. En 2 casos los padres no autorizaron la transfusión. Se realizaron un total de 8 transfusiones intravasculares a los 5 casos restantes, y a 2 de éstos se realizaron transfusiones de forma repetida. Conclusiones. la transfusión intravascular es el método de elección para el tratamiento de la anemia fetal en nuestro medio. Tras iniciarse en el año 2007 el uso de este tratamiento, se ha podido realizar en todos los casos en que se encontraba indicado(AU)
Objectives. to present intrauterine intravascular transfusions cases performed for fetal anaemia in Fetal Medicine Unit of Canaries University Hospital Maternity Ward. Material and method. prospective descriptive study of cases diagnosed of fetal anaemia that were treated with intrauterine transfusion from may 2007 to June 2009. Results. during this period seven cases of fetal anaemia were diagnosed. Four isoimmunization-anaemia and three of non-immune anaemia. Eight intrauterine transfusions were performed in five of cases (in two cases repeated transfusion was required). Two cases did not allow transfusion. Conclusion. blood transfusion through umbilical cord seems to be the best option for fetal anaemia treatment. After first intrauterine transfusion in 2007, all indicated cases were carried out(AU)