HAEMOCHROMATOSIS

DEFINITION

Haemosiderosis is the deposition of hemosiderin (iron); haemochromatosis is the disease caused by iron deposition.

AETIOLOGY

Disease may be primary or secondary (e.g. chronic transfusion therapy like in beta-thalassemia major)

GENETICS

Associated with HLA A3 Primary haemochromatosis due to C282Y or

H63D mutation on HFE geneo C282Y Homozygote – most will

accumulate iron, only a minority will develop symptoms. Men are affected more often than women

o H63D homozygote – Most have normal iron levels. A few may develop iron overload. Not as bad as C282Y Homozygote

o Compound Heterozygote (C282Y and H63D) – Most have normal iron levels. Moderate iron overload can develop. Severe iron overload may occur if there are other risk factors e.g. alcoholism or viral hepatitis.

o C282Y heterozygote – about 10% of white people have this genotype; most have normal iron levels

o H63D heterozygote- About 20% of white people have this genotype. Very unlikely to cause iron overload seek another cause.

CLASSIC PRESENTATION

Triad of:o Micronodular cirrhosiso Diabetes Mellituso Skin Pigmentation “Bronze Diabetes”

Can also result in:o CHFo Testicular atrophyo Increased risk of hepatocellular

carcinoma

Hereditary form is normally asymptomatic until late stages of the disease. Symptoms usually start between ages 30-50.

INVESTIGATIONS

Increase in ferritin, iron and decreased TIBC Transferrin saturation will increase

o Normally this will occur first

TREATMENT OF HEREDITARY HAEMOCHROMATOSIS

Repeated phlebotomy Deferasirox Deferoxamine