Inherited disorders of iron metabolism.

Abstract

Recent molecular studies have resulted in the identification of genetic alterations underlying hereditary disorders of iron metabolism. One example is the discovery of the HFE gene that is mutated in patients suffering from hereditary hemochromatosis. This autosomal recessive disorder has an estimated carrier frequency that varies between 0.07 and 0.13, thus representing one of the most common genetically determined metabolic disorders. The identification of the hemochromatosis mutations has encouraged efforts to investigate other conditions with iron overload for a putative interaction with these genetic variants. Few data are already available suggesting, for example, that iron overload in patients with sporadic porphyria cutanea tarda is associated with mutations in the hereditary hemochromatosis gene. However, it is obvious that disorders of iron metabolism have a multifactorial pathogenesis, including environmental and genetic factors. Thus, many questions remain to be answered about whether a genetic predisposition exists for development of various iron-loading or iron-deficiency phenotypes. This review focuses on the most recent advances in the field of hereditary disorders of iron metabolism and discusses their potential implications for nephrologists.