Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis

Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France).

For the half of these predisposed subjects, the phenotypic expression of the disease needs a treatment. This treatment is based upon repeated bloodletting which is generally considered as simple, safe and effective.

Nevertheless, it is still questioned as regard its physiopathological justification and its clinical implications. Indeed, bloodletting could cause an increase of non-transferrin bound iron (NTBI) particularly for its reactive form called labile plasma iron (LPI) This adverse physiopathological effect could have clinical consequences and could be linked with articular consequences which can be aggravated by the treatment.

Hemochromatosis type 1 is one of the most frequent genetic disease since the genetic predisposition (homozygosity for the C282Y mutation of the HFE gene) is encountered in about 3/1000 white subjects (5/1000 in Brittany, France).

For the half of these predisposed subjects, the phenotypic expression of the disease needs a treatment. This treatment is based upon repeated bloodletting which is generally considered as simple, safe and effective.

Nevertheless, it is still questioned as regard its physiopathological justification and its clinical implications. Indeed, bloodletting could cause an increase of non-transferrin bound iron (NTBI) particularly for its reactive form called labile plasma iron (LPI) This adverse physiopathological effect could have clinical consequences and could be linked with articular consequences which can be aggravated by the treatment.

The primary objective is to explore the effect of bloodletting upon plasmatic concentrations of NTBI.

The secondary objectives are to:

* explore the impact of bloodletting upon different parameters of iron metabolism and in particular LPI, hepcidinemia and markers of erythropoiesis ;
* explore basal and nycthemeral characteristics of new parameters of iron metabolism (hepcidin, NTBI, LPI) in hemochromatosis patients.

The demonstration of an adverse effect of bloodletting upon iron metabolism would allow for a therapeutic innovation based upon an association of bloodletting and oral chelation during the induction treatment of type 1 hemochromatosis and, more generally in hepcidino deficient forms of hemochromatosis.

Eligibility Criteria:
Inclusion Criteria:

* Men
* Age 18 years or older
* Homozygosity for the C282Y mutation of the HFE gene
* With an indication of treatment by bloodletting (in accordance with the French HAS guidelines)
* Ferritinemia ≥ 500µg/L
* Transferrin saturation ≥ 75%
* Never treated by bloodletting
* Written informed consent

Exclusion Criteria:

* Contraindication to bloodletting
* Chronic inflammatory or dysmetabolic or neoplastic disease
* Major cardiovascular disease
* Excessive consumption of alcohol (≥ 3gr/day)
* Treatment by iron chelators, C or E vitamins
* Stay in altitude\> 1500m in the month preceding the period Day 1
* Patients under guardianship
* Blood donation in the 3 past months
* Night / shift workers