Cohort of Patients With Rare Iron Overloads Excluding C282Y Homozygosity

Chronic iron overload are responsible for morbidity and mortality. There are many causes, genetic and acquired. Hepcidin deficiency related to genetic desease is one of them.

This study concerns specifically this cause, and seeks to characterize these iron overloads on clinical, biological, genetic and functional point of view.

A significant number of patients with chronic iron overload, present a phenotype of hepcidin deficiency. This profile is characterized by an elevated plasma iron increased serum transferrin saturation, a transferrin saturation, and a parenchyma distribution of iron overload. These diseases either remains unexplained or are associated with mutations in the gene involved in iron metablism regulation.

The main objective of this study is to characterize these iron overloads with phenotype of hepcidin deficiency not related to homozygosity C282Y (clinical, biological and genetic).

• samples with DNA (Other)

Primary outcomes

• Number of patients presenting with mutation in gene know to be associated with iron metabolism [Inclusion]: to characterize these iron overloads with phenotype of hepcidin deficiency not related to homozygosity C282Y (clinical, biological and genetic).

Secondary outcomes

• comparison of the hepcidin and hepcidin/ferritin ratio in patient with or without in gene known to be associated with iron metabolism [inclusion]: To Identificate potential explanatory factors of hepcidino deficiency phenotype
• Number of patients presenting with associated causes of iron overload [inclusion]: \- Identification of potentially explanatory factors visceral consequences of iron overload in hepcidino deficiency phenotype (overweight, high blood pressure, diabetes)
• Genotype-Phenotype correlation [Inclusion]: To Research correlations genotype-phenotype
• Hepatic and splenic iron concentration measurements by NMR [Inclusion]: Validation of the hepatic iron concentration measurements imaging ( nuclear magnetic resonance (NMR)) in the various centers
• Number of patients with detectable abnormal iron species in blood (non transferrin bound iron, labile pool iron) [Inclusion]: \- Assessment of the clinical value of biomarkers of iron metabolism

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Biological profile suggestive of hepcidin deficiency:

  * increase of transferrin saturation coefficient (> 50 %) verified on at least 2 times, and calculated from the transferrinemia.
  * Proved hepatic iron overload: by the dosage of the iron hepatic concentration either on block hepatic biopsic, or by MRI according to the method of quantification of the iron validated overload (by adopting a threshold of 100 µmol /g)
  * Patient's written consent for examination of genetic characteristics for diagnosis and collection development for genetic and not genetic research within the framework of an abnormality of the iron metabolism
  * Patient written inform consent.

Exclusion Criteria:

* HFE hemochromatosis: homozygosity C282Y/C282Y
* Treatment with iterative phlebotomy
* Hematologic diseases with dyserythropoiesis and/or repeated transfusions
* Haptoglobin low, below normal directing towards the diagnosis of chronic hemolysis, myelodysplasia
* Prolonged oral or parenteral iron supplementation
* Current or past excessive regular drinking
* Patient minor or under legal protection measure

• Edouard BARDOU-JACQUET, MD/PhD, Principal investigator, CHU Pontchaillou