D. Girelli

A linkage between hereditary hyperferritinaemia not related to iron overload and autosomal dominant congenital cataract

Summary. The only genetic disorder with elevated serum ferritin levels so far described is hereditary HLA‐related haemochromatosis. On the other hand, hereditary cataract is both genotypically as well as phenotypically heterogenous, and no specific locus or any useful marker has been yet identified. We studied two Italian families in whom a combination of elevated serum ferritin not related to iron overload and congenital nuclear cataract is transmitted as an autosomal dominant trait. Affected individuals have normal serum iron and transferrin saturation, but high serum ferritin. Red cell counts are normal and venesection therapy rapidly produces iron‐deficiency anaemia.

1133 A TIME COURSE OF HEPCIDIN RESPONSE TO ORAL IRON CHALLENGE IN HFE AND TFR2 HEMOCHROMATOSIS PATIENTS

Background. Inadequate hepcidin production leads to iron overload in nearly all types of haemochromatosis. We explored the acute response of hepcidin to iron challenge in 25 patients with HFE-haemochromatosis, in 2 with TfR2-haemochromatosis and in 13 controls. Sixteen patients (10 C282Y/C282Y, 6 C282Y/H63D compound heterozygotes) had increased iron stores, while 9 (6 C282Y/C282Y, 3 C282Y/H63D) were studied after phlebotomy-induced normalization of iron stores. nnDesign and Methods. We analyzed serum iron, transferrin saturation, and serum hepcidin by both ELISA and mass-spectrometry at baseline, 4, 8, 12 and 24 hours after a single 65-mg dose of oral iron. nnResults. Serum iron and transferrin saturation significantly increased at 4 and returned to baseline at 8-12 hours in all groups, except in the iron-normalised patients who showed the highest and longest increase of both parameters. Hepcidin increased significantly at 4 and returned to baseline at 24 hours in controls and in C282Y/H63D compound heterozygotes at diagnosis. Hepcidin response was smaller in C282Y-homozygotes than in controls, barely detectable in iron-depleted HFE- and absent in TfR2-patients. nnConclusions. Our results are consistent with a scenario in which TfR2 plays a prominent and HFE a contributory role in hepcidin response to a dose of oral iron. In iron-normalised HFE-patients, both the low hepcidin baseline and the weak response to iron contribute to hyperabsorption of iron.