Hereditary Hemochromatosis C282Y Homozygous
Conditions
Keywords
hereditary hemochromatosis C282Y homozygous, Iron Reabsorption Index (IRI), Hepcidin / ferritin (H / F) ratio
Brief summary
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.
Detailed description
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.
Interventions
None listed
Sponsors
Rennes University Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men, at least 18 years old * hereditary hemochromatosis C282Y homozygous diagnosed and followed in the service of Liver Diseases, University Hospital of Rennes * Maintenance therapy with phlebotomy for at least 1 year with stable iron stock on the basis of at least four previous plasma ferritin \< 50μg / L, * Written, free and informed consent
Exclusion criteria
* Intercurrent illness unrelated to hemochromatosis causing cytolysis or inflammatory reaction. * Person with a measure of legal protection (guardianship)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| distribution of values of Hepcidin / ferritin plasma ratio | First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time | values of Hepcidin / ferritin plasma ratio |
Secondary
| Measure | Time frame |
|---|---|
| Correlation between Hepcidin / ferritin plasma ratio and IRI. | First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time |
| Correlation between Hepcidin / Ferritin ratio before and after treatment | First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time |
| Distribution of inter-individual Hepcidin / Ferritin ratio according to the stage of liver fibrosis | First dosage on an empty stomach at current time of phlebotomy (Day 0), second dosage at day 14 at the same time, third dosage at day 28 at the same time, fourth dosage at day 42 at the same time, fifth dosage at day 56 at the same time |
Countries
France
Outcome results
None listed