Hereditary Haemochromatosis

Hereditary Haemochromatosis (HH)

= inherited disease characterized by excess iron deposition in various organs leading to eventual fibrosis and functional organ failure.

Main types of inherited disorder:
- Type 1. HFE gene
- Type 2A. Juvenile HJV gene
- Type 2B. Juvenile HAMP gene
- Type 3. TfR2 gene
- Type 4. SLV40A1 gene

Mechanism of damage

I. HFE gene protein interacts with the transferrin receptor 1 (=mediator in intestinal iron absorption) leading to iron being taken up by the muscosal cells inappropriately, exceeding binding capacity.
II. Hepcidin is a protein that controls iron absorption. Mutations mentioned above disrupt hepcidin expression leading to uninhibited iron overload.

Clinical features

- Bronze skin pigmentation
- Hepatomegaly
- Diabetes mellitus
- Hypogonadism (secondary to pituitary dysfunction)
- Cardiac manifestation; heart failure, arrhythmias.
Complications; 30% will develop primary hepatocellular carconoma (HCC)

Investigation

- Serum iron; elevated.
- Serum ferritin; elevated.

Liver biopsy; to assess extent of tissue damage, assess tissue iron, and measure the hepatic iron concentration.

Treatment

- Venescetion
- Chelation therapy with desferrioxamine.