CLINICAL AND GENETIC CHARACTERISTICS OF A PROSPECTIVENONHFE C282Y HEMOCHROMATOSIS COHORT

Background:

Rare hemochromatosis are mainly described using retrospective study and cases reports. A new consensus classification allows diagnosis encompassing broader definition. We aimed to describe a nationwide prospective cohort of patients with non HFE C282Y hemochromatosis.

 

Method:

Patients with Saturation>50% and Liver iron content >100µmol/g, without secondary causes of iron overload were prospectively included in ten centers. Liver iron content (LIC) MRI interpretation, biochemical test for iron metabolism and Next generation sequencing panel (HFE, HAMP, TF, TFR2, HJV, SLC40A1, BMP6, CP) were performed centrally.

 

Results:

119 patients (75.6% male, age 57years±13) were included. 44 patients had C282Y/H63D compound HFE heterozygosity and 16 were C282Y HFE heterozygotes. Ferritin levels were 1417µg/L±1417, transferrin saturation was 60.3%±19.2, LIC was 200µmol/g±108. Mean hepcidin/ferritin ratio was 2±1.4, significantly lower than in healthy volunteers. Non transferrin bound iron (NTBI) was present in 98 patients (mean=1.25µmol/L±0.9) and LPI was present in 76 patients (mean=0.23µmol/L±0.4). LPI was significantly correlated to hepcidin/ferritin ratio, LIC and liver enzymes.

25 patients had definite diagnosis (10 HFE related and 15 non HFE related), 27 had variant of unknown significance of which had 19 putative digenic hemochromatosis. Eventually 68 patients had molecularly undefined hemochromatosis. Patient with definite diagnosis had significantly higher ferritin, LIC, NTBI and LPI.

 

Conclusion: 

Our results suggest that current genetic panel testing methods yields definite diagnosis in only half of patients with non HFE c282y hemochromatosis, and that the hepcidin/ferritin ratio can be useful to assess the severity of hemochromatosis and confirm hepcidin deficiency.