Functional and clinical implications of ferroportin mutation p.Arg178Gln

Abstract

Ferroportin disease is an autosomal dominant iron storage condition with different phenotypic expression, where a clear genotype to phenotype correlation has been reported for selected mutations. Ferroportin disease is primarily caused by private mutations in the gene SLC40A1, which encodes an iron export protein. Genetic defects can cause a loss of iron export function which is typically associated with low transferrin saturation and hepatolienal siderosis. In contrast a gain of function is usually associated with high transferrin saturation and hepatic siderosis, where the spleen is unaffected. Liver disease has been described primarily in the latter group of patients. The toxic effect of stored iron in patients with loss of function mutations is apparently mild.