Ferroportin disease (
hemochromatosis type 4) is a recently recognized disorder of human
iron metabolism, characterized by
iron deposition in macrophages, including Kupffer cells. Mutations in the gene encoding
ferroportin 1, a cellular
iron exporter, are responsible for this
iron storage disease, inherited as an autosomal dominant trait. We present clinical, histopathological, and radiological findings in a family with the most common
ferroportin mutation, V162del. In the index case, the disorder is characterized by abundant deposition of
hemosiderin in all tissues investigated (mesenteric lymph node, liver, gastric and duodenal mucosa, and also in
squamous cell carcinoma of the lung). The radiological findings indicated the presence of excess
iron in bone marrow and spleen. Despite a significant burden of
iron, no features of chronic
liver disease were found in affected members of the family, including individuals aged up to 80 years.
Hyperferritinemia greater than 1,000 microg/L was a penetrant biochemical finding before the second decade in life and was associated with significantly increased serum concentrations of
pro-hepcidin that correlated positively with urinary
hepcidin concentrations. In conclusion, the systemic
iron burden in
ferroportin disease is not a sufficient cause for chronic
liver disease. In patients with most, but not all,
ferroportin mutations, retention of
iron in macrophages of the liver and other organs may protect against damage to parenchymal cells. Finally, macrophage
iron storage in
ferroportin disease is associated with elevated serum
pro-hepcidin levels.