Hereditary Hemochromatosis C282Y Homozygous Clinical Trial
Official title:
HEPFER-Evaluation of a New Phenotypic Biological Marker in Genetic Type 1 Hemochromatosis
HFE(High iron FE)-related hereditary hemochromatosis has a highly variable penetrance. No
phenotypic or genetic markers can predict the disease. The Iron Reabsorption Index (IRI),
recently described by our group, correspond to the daily reabsorbed iron for a subject whose
iron stock is stable and less than 50 µg / L.
The IRI is constant over time, reflecting the importance of the underlying functional
deficit.
Hepcidin / ferritin (H / F) ratio may be an independent and constant over time marker of
disease stage.No data are available on the validated values of this ratio.
The goal of this project is to determine the intra-individual variations of the H / F ratio
over time during maintenance therapy and to assess the correlation with the IRI.
HFE-related hereditary hemochromatosis has a highly variable penetrance : 1% of homozygous
women and 30% of homozygous men would develop a clinically expressed disease. No predictive
phenotypic or genetic markers are available.
The Iron Reabsorption Index (IRI), recently described by our group, correspond to the daily
amount of reabsorbed iron for a subject whose iron stock is less than 50 µg / L and
stabilized with maintenance phlebotomy.
For one patient, the IRI is constant over time, probably related to the functional deficit
underlying. Unfortunately, IRI is a retrospective marker requiring at least one year of
treatment, which limits its practical interest and directs its use for research activity.
We're looking for a more simple phenotypic marker readily available in clinical practice,
which would predict at the time of diagnosis the evolution of the disease and therefore
would better define the therapeutic options.
The pathophysiology of hemochromatosis is a dysregulation of hepcidin synthesis. We assume
that hepcidin / ferritin ratio could be a phenotypic marker like the IRI, stage disease
independent and constant over time. Indeed H/F ratio may reflect the adaptability of
hepcidin production regulation for a level of iron stock No data are available on the
validated values of this ratio. The aim of the project is to determine the intra-individual
variations of the H / F ratio over time during maintenance therapy and to assess the
correlation with the IRI.
The study involve 30 C282Y homozygous men, followed in a reference center with phlebotomy
maintenance therapy and stabilized at a low level of ferritin (<50 µg / L) for at least 1
year.
The intra-individual variation of H/F ration will be determine by 5 samples every 14 days
for 8 weeks. The correlation with IRI will be validated externally by the iron load observed
at diagnosis. We will take into account other known variation factors like liver damages
associated with hemochromatosis at diagnosis.
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Observational Model: Cohort, Time Perspective: Prospective