In a patient with hereditary hemochromatosis due to HFE C282Y homozygosity, hepcidin is inappropriately low relative to body iron overload. What is the primary molecular consequence of hepcidin deficiency at the level of the enterocyte and macrophage?

• A Uncontrolled ferroportin-mediated iron export from enterocytes and macrophages into plasma ✓
• B Increased expression of DMT1 at the apical membrane of enterocytes
• C Failure of ferroportin translation due to lack of iron-responsive element binding
• D Increased expression of hephaestin, the ferroxidase at the basolateral membrane

Explanation

Hepcidin binds ferroportin on enterocytes, macrophages, and hepatocytes, causing its internalization and degradation. When hepcidin is deficient as in HFE hemochromatosis, ferroportin remains constitutively active on the cell surface, allowing unregulated iron export from enterocytes (increasing dietary absorption) and from macrophages (increasing plasma iron recycling). This is the central mechanism of iron overload in hemochromatosis. Option B is wrong because DMT1 expression is regulated separately by iron status via IRP/IRE. Option C is wrong because ferroportin is translated but not degraded. Option D is a distractor; hephaestin is a copper-dependent ferroxidase, not regulated by hepcidin.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.