Rare Iron Overloads Except C282Y Homozygosity : Description and Characterization.

Clinical, Biological, Genetic and Functional Characterization of Rare Iron Overload Phenotypes Associated With Hepcidin Deficiency Except C282Y Homozygosity.

Chronic iron overload is responsible for morbidity and mortality. There are many genetic and acquired causes. One of them is an hepcidin deficiency. Hepcidin is the regulating hormone for iron. The study explores this specific cause, and aim to characterize this iron overload in term of clinical, biological, genetic and functional specificities.

One of chronic iron overload profiles is a deficit in hepcidin. Hepcidin is the regulating hormone for iron. This specific profile is characterized by an elevated serum iron, an elevated transferrin saturation, and parenchymal damages of iron overload. This disease is not connected with known mutations of iron metabolism genes.

The main objective of this study is the clinical, biological, genetic and functional characterization of rare iron overload phenotypes associated with hepcidin deficiency except C282Y homozygosity.

Inclusion criteria:

• Biological profile suggesting hepcidin deficiency:

  • high serum iron (> 25μmol / l) checked at least 2 times.
  • increased transferrin saturation coefficient (> 50 %) checked at least 2 times, and calculated from transferrinemia.

• Proved hepatic iron overload: using a dosage of iron hepatic concentration either on hepatic biopsy, or by MRI according to the method of iron overload quantification. A threshold of 100 µmol / g is set.

• Patient's written consent for examination and collection of genetic data to set the diagnosis.

Non inclusion criteria:

• HFE hemochromatosis: C282Y/C282Y homozygosity
• Treatment by iterative phlebotomies (more than 2 phlebotomies)
• Hematological diseases with dyserythropoiesis and/or repeated transfusions
• Low haptoglobin level, suggesting chronic hemolysis or myelodysplasia
• Long-term iron oral and/or parenteral supplementation