Review article: the iron overload syndromes

Abstract

Summary Background Iron overload syndromes encompass a wide range of hereditary and acquired conditions. Major developments in the field of genetics and the discovery of hepcidin as a central regulator of iron homeostasis have greatly increased our understanding of the pathophysiology of iron overload syndromes. Aim To review advances in iron regulation and iron overload syndrome with special emphasis on hereditary haemochromatosis, the prototype iron overload syndrome. Methods A PubMed search using words such as ‘iron overload’, ‘hemochromatosis’, ‘HFE’, ‘Non‐HFE’, ‘secondary iron overload’ was undertaken. Results Iron overload is associated with significant morbidity and mortality. Sensitive diagnostic tests and effective therapy are widely available and can prevent complications associated with iron accumulation in end‐ organs. Therapeutic phlebotomy remains the cornerstone of therapy for removal of excess body iron, but novel therapeutic agents including oral iron chelators have been developed for iron overload associated with anaemia. Conclusions Iron overload disorders are common. Inexpensive screening tests as well as confirmatory diagnostic tests are widely available. Increased awareness of the causes and importance of early diagnosis and knowledge of the appropriate use of genetic testing are encouraged. The availability of novel treatments should increase therapeutic options for patients with iron overload disorders.

Mössbauer spectroscopy of the iron cores in human liver ferritin, ferritin in normal human spleen and ferritin in spleen from patient with primary myelofibrosis: preliminary results of comparative analysis

“…However, there are a number of diseases, so called ''iron overload disease'' related to increase in total body iron stores. Iron overload can be classified as primary or secondary depending whether it results from a primary defect in the regulation of iron balance or is secondary to other genetic or acquired disorders (see Piperno 1998;Fleming and Ponka 2012;Siddique and Kowdley 2012). The presence of iron in iron storage proteins permits to apply Mössbauer spectroscopy for analysis of the iron content and state in these proteins and tissues containing ferritin (see, for instance, St.…”

Zieve's Syndrome and Hemochromatosis, are they Related?

“…The diagnosis requires exclusion of viral, autoimmune hepatitis and biliary obstruction; negativity of serologic and autoimmune markers. Hemochromatosis is an abnormal accumulation of iron in parenchymal organs of the body that leads, if not treated to organ dysfunction [4,5]. Iron overload syndromes are divided into two main groups (Tables 1 and 2).…”

Mutações genéticas, métodos diagnósticos e terapêuticas relacionadas à hemocromatose hereditária

“…Em 1889, Von Recklinghausen, patologista alemão, usou o termo "hemocromatose" após descobrir que os pacientes tinham uma pigmentação nas células do fígado provocada pelo ferro. Sheldon (1935, apud SIDDIQUE;KOWDLEY, 2012) tornou claro que a doença era hereditária e causada por excesso de depósitos de ferro nos tecidos e a associou com desordens do metabolismo do ferro (PIETRANGELO, 2004;SIDDIQUE;KOWDLEY, 2012). Com o decorrer dos estudos, Simon et al (1976) deiniram a incidência e transmissão genética da doença que parecia estar ligada ao complexo HLA e mapeado próximo ao lócus do HLA-A.…”

“…Com o decorrer dos estudos, Simon et al (1976) deiniram a incidência e transmissão genética da doença que parecia estar ligada ao complexo HLA e mapeado próximo ao lócus do HLA-A. Foi então em 1996, que Feder identiicou o gene da HFE, para a mutação (C282Y) que estava presente na maioria dos pacientes com HH (PIETRANGELO, 2004;SIDDIQUE;KOWDLEY, 2012). Esta alteração hereditária no gene da HH leva ao acúmulo progressivo do ferro nas células parenquimatosas do fígado, pâncreas e coração (VILLANI et al, 2010).…”

“…Ela deve ser considerada apenas com a inalidade de determinar a presença ou ausência da ibrose avançada ou cirrose, que não possui valor diagnóstico para hemocromatose (BACON et al, 2011;SIDDIQUE;KOWDLEY, 2012 Outro parâmetro utilizado para a quantiicação do ferro no miocárdio é a do T2*. A doença cardíaca é a principal causa de morte em pacientes com sobrecarga de ferro.…”