July 7, 2020
Hereditary Haemochromatosis (HH) Minimize

Hereditary haemochromatosis (HH)

Haemochromatosis is an inherited condition in which too much iron is absorbed from the diet. Iron accumulation in many organs causes the clinical manifestations including diabetes and cirrhosis of the liver. Clinical problems are usually seen in middle age but sometimes occur in people as young as 20 years. Haemochromatosis is inherited as an autosomal recessive disorder. The excess iron is removed by weekly venesections for up to 2 years. If the diagnosis is made before the development of cirrhosis of the liver, iron removal usually prevents the clinical problems and restores normal life expectancy.

Clinical features of haemochromatosis

In early disease there may be no diagnostic features. However, all tissues are affected by iron deposition which results in skin pigmentation, diabetes mellitus, liver and cardiac disease, arthropathy and primary and secondary hypogonadism.

Diagnosis of iron overload

The diagnosis of haemochromatosis is made on the demonstration of transferrin saturation > 55% (men) or > 50% (women) on two samples of which one should be fasting; [transferrin saturation = (Fe/TIBC) x 100%]. A diagnosis of haemochromatosis is only made in a proportion of subjects with raised non-fasting transferrin saturation. Ferritin concentration is usually elevated, particularly in the presence of liver disease, but may be normal in the early stages of iron accumulation. Confirmation may be made by liver biopsy. 

Following the demonstration of iron overload, secondary causes of iron overload need to be excluded before haemochromatosis can be diagnosed. These include porphyria cutanea tarda, beta thalassaemia intermedia, hereditary spherocytosis and sideroblastic anaemia. False positive raised transferrin saturation may be due to fatty liver, alcoholic liver disease and haematological conditions. 

Liver iron determination

Liver biopsies (3-10 mg wet weight) should be transferred to the laboratory in dry containers as quickly as possible for accurate measurement of weight. Hepatic iron is classified as an hepatic iron index (Fe micromol/ gm dry weight divided by the age in years). Liver biopsy is not necessary for the diagnosis if mutations in the HFE gene are present, but may be useful to assess hepatic fibrosis. 

Monitoring efficacy of venesection

Venesection should be performed sufficiently frequently to maintain plasma transferrin saturation below 60% and the ferritin concentration below 100 ng/mL.

Genetic tests for the proband and family members

90% of UK patients are homozygous for the Cys282Tyr mutation in the HFE gene. This mutation is present in approx 1:250 of the UK population and its analysis together with iron studies can be used for screening families where a proband has been identified. It is unknown how many subjects homozygous for the Cys282Tyr mutation will eventually develop clinical haemochromatosis.


Niederau C, Fischer R, Purschel A, Stremmel W, Haussinger D, Strohmeyer G. Long term survival in patients with hereditary haemochromatosis. Gastroenterol 1996;110:1107-1119.

Dooley J, Worwood M. Genetic haemochromatosis. British Committee for Standards in Haematology. British Committee for Standards in Haematology. Darwin Medical Communications, Oxford. 2000.


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