Hemochromatosis

Work in progress!

Hemochromatosis is a hereditary disorder that leads to an iron overload in organs due to an increased iron absorption from food. It is caused by a point mutation in the HFE gene.

Phenotype

The hemocromatosis phenotype and its harmfulness varies in patients. Symptoms are caused by a toxic iron accumulation in parenchymal cells of important organs, e.g. heart, liver, endocrine glands. Based on the affected organs, the symptoms range from gonadal dysfunction, glucose intolerance, diabetes, heart failure to liver fibrosis and cirhosis.

Biochemical disease mechanism

The basis for hemocromatosis is a hepcidin deficiency. Hepcidin is a protein that is responsible for the downregulation of iron entry into the bloodstream. Patients do not suffer from a perturbance of the iron metabolism, which works normal, but from an increased iron uptake into the blood.

Iron Metabolism

Iron is only able to enter the human body in the small intestines.

Genetics

There are several different types of hemochromatosis. Each type is connected to defects in the iron uptake regulation through hepcdin. The most common and less severe type is caused by a mutation in the HFE gene on chromosome 6. The other types are rare and based on a mutations in the TfR2 gene or, in the case of juvenile hemochromatisis, mutations in the HJV or HAMP (Hepcidin) gene. Mutations in the FPN(Ferroportin) gene can also result in hemachromatosis like symptoms. The mutations leads to a hepcidin resistance and thus to an iron hyperabsorbtion from the diet, although the hepcidin production is not impaired in this patients.

Mutations

HFE: C282Y
TfR2: Y250X (nonsense)
HJV: G320V
HAMP:
FPN: C326S and C326Y

Treatment

Since iron can only be removed from the system by blood loss, treatment is complicated. Possible treatment is only used to reduce the iron content in the body. A low iron diet