Iron and
copper are
trace elements essential for health, and
iron metabolism is tightly regulated by cuproproteins. Clarification of the interactions between
iron and
copper may provide a better understanding of the pathophysiology and treatment strategy for
hemochromatosis,
Wilson disease, and related disorders. The
hepcidin/
ferroportin system was used to classify genetic
iron overload syndromes in Japan, and
ceruloplasmin and ATP7B were introduced for subtyping
Wilson disease into the severe hepatic and classical forms. Interactions between
iron and
copper were reviewed in these
genetic diseases.
Iron overload syndromes were classified into pre-hepatic
iron loading
anemia and
aceruloplasminemia, hepatic
hemochromatosis, and post-hepatic
ferroportin disease. The ATP7B-classical form with
hypoceruloplasminemia has primary hepatopathy and late extra-hepatic complications, while the severe hepatic form is free from ATP7B mutation and
hypoceruloplasminemia, and silently progresses to
liver failure. A large amount of
iron and trace
copper co-exist in hepatocellular dense bodies of all
iron overload syndromes. Cuproprotein induction to stabilize excess
iron should be differentiated from
copper retention in
Wilson disease. The classical form of
Wilson disease associated with suppressed hepacidin25 secretion may be double-loaded with
copper and
iron, and transformed to an
iron disease after long-term
copper chelation.
Iron disease may not be complicated with the severe hepatic form with normal
ferroxidase activity. Hepatocellular dense bodies of
iron overload syndromes may be loaded with a large amount of
iron and trace
copper, while the classical
Wilson disease may be double-loaded with
copper and
iron.