HAMP and hyperinsulinemic hypoglycemia, familial, 4: This suggests that: (i) synovial iron deposition [103] may represent an inaccessible compartment for iron depletion by venesections because synovial fluid is not contiguous with serum; (ii) synovitis, that has been documented in hemochromatosis [104,105] is irreversible despite effective iron depletion; and/or (iii) hepcidin deficiency leading to iron excess could be involved directly in symptomatic arthropathy and/or (iv) the mutations of the HFE gene, that encodes an HLA-like class I protein, could be involved directly in disease expression [106].