Lack of enterocyte iron accumulation in the ferroportin disease.
Ferroportin-associated iron overload (also known as the ferroportin disease) is a common cause of hereditary hyperferritinemia. It was originally proposed that loss-of-protein function mutations account for iron overload in the FD. This hypothesis is consistent with the phenotype reported in most patients with FD of early iron accumulation in tissues, particularly in macrophages, in spite of relatively normal-low circulatory iron. It was still unclear, however, how FPN mutations would affect iron retention in enterocytes. We studied histologically the intestine of six patients with different FPN mutations as compared to other subjects with various iron disorders. We found that regardless of the underlying FPN mutation, no iron accumulation was found in absorbing enterocytes while, intestinal villi showed marked signs of iron accumulation in the cells of lamina propria. Not surprisingly, in the liver, iron excess was found mainly in Kupffer cells. These results indicate that FPN haploinsufficiency is not limiting for iron export from enterocytes.
Corradini
Elena
E
Center for Hemochromatosis, Department of Internal Medicine, University of Modena Policlinico Via del Pozzo 71 41100 Modena, Italy.
Montosi
Giuliana
G
Ferrara
Francesca
F
Caleffi
Angela
A
Pignatti
Elisa
E
Barelli
Samuele
S
Garuti
Cinzia
C
Pietrangelo
Antonello
A
D000328:Adult; D000368:Aged; D027682:Cation Transport Proteins / Q000235:genetics*; D020895:Enterocytes / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019190:Iron Overload / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D007728:Kupffer Cells / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000098742:Ferroportin
D027682:Cation Transport Proteins; D000098742:Ferroportin; D007501:Iron