Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.
Curr Opin Pediatr. 2011 Feb;23(1):14-20. doi: 10.1097/MOP.0b013e3283425591.
To discuss inherited iron disorders, their pathophysiology and clinical implications in the light of the recent advances in our knowledge of iron metabolism and its regulation.
In previous years the molecular mechanisms of cellular iron uptake and release and the cellular and systemic iron homeostasis have been substantially clarified. New proteins (hepcidin, hemojuvelin, HFE, TFR2 and ferroportin), mutated in hereditary hemochromatosis, have been identified with a crucial role in iron regulation. These advances have modified our understanding of the pathophysiology of hemochromatosis, now considered a disorder either due to hepcidin deficiency or (rarely) due to hepcidin resistance. Novel genetic forms of iron-related microcytic anemia have been identified, due to defects of iron transport/utilization or to TMPRSS6 deficiency and hepcidin hyperproduction, as occurs in iron-refractory iron deficiency anemia (IRIDA). A role for hepcidin has been identified also in acquired conditions, as in iron-loading anemias and in anemia of chronic diseases and inflammation.
Advances in basic research have improved the classification and diagnosis of genetic anemias and iron overload and are paving the way towards the development of drugs that target the molecular lesions.
根据近年来对铁代谢及其调节的认识进展，讨论遗传性铁代谢疾病及其病理生理学和临床意义。
近年来，细胞铁摄取和释放的分子机制以及细胞和全身铁稳态已得到充分阐明。新的蛋白质（铁调素、幼血红素蛋白、HFE、TFR2 和亚铁蛋白）在遗传性血色素沉着症中发生突变，在铁调节中起关键作用。这些进展改变了我们对血色素沉着症病理生理学的理解，现在认为它是由于铁调素缺乏或（很少）由于铁调素抵抗引起的疾病。由于铁转运/利用缺陷或 TMPRSS6 缺乏和铁调素过度产生，导致新型遗传性小细胞性贫血的基因形式，如铁难治性缺铁性贫血（IRIDA）。铁调素在获得性疾病中也有作用，如铁负荷性贫血和慢性病和炎症性贫血。
基础研究的进展提高了遗传性贫血和铁过载的分类和诊断水平，并为针对分子病变的药物开发铺平了道路。
