Last updated: Friday, 03, December, 2010
Common, autosomal recessive disorder of iron absorption, with progressively increasing iron stores and organ damage. Not all patients with the genetic abnormalities may be symptomatic, but they remain at risk for cirrhosis and other end organ damage.
Juvenile haemochromatosis is a different disease.
Iron studies: Ferritin, Serum Iron / iron binding capacity to assess transferrin saturation (TF%).See Table 3 Interpretation of the results of iron studies
HFE mutation analysis: PCR for C282Y, H63D and S65C mutations.
The C282Y mutation is responsible for 85 - 90% of haemochromatosis cases in persons of European origin. The role of the H63D and the S65C mutation is less clear though C282Y / H63D compound heterozygotes may demonstrate iron overload.
Liver biopsy: may sometimes be required to diagnose and provide prognostic information in haemochromatosis. Used to assess hepatic iron index and for the presence of fibrosis / cirrhosis.
In the setting of C282Y homozygosisty, with normal AST, a ferritin of X1000 microg/L, no evidence of hepatomegaly and no additional risk factors for liver disease (eg alcohol) a biopsy is NOT required.
Family studies: should be performed. Siblings have a 25% chance of having haemochromatosis if one parent has genetic haemochromatosis.
Screening for Haemochromatosis:
A random TF% > 45% should be confirmed on a repeat fasting sample.
A number of differing screening approaches have been advocated, based on TF% action thresholds ranging between 45% and 62% with differing diagnostic sensitivities.
A persistent fasting TF% >45% in males or >40% in females suggest iron accumulation andmay require further investigation.
If ferritin is elevated with normal or low transferrin saturation, consider a reactive increase in ferritin associated with liver disease, infection, inflammation or malignancy. Ferroportin disease should also be considered.
Dooly J and Worwood M, British Committee for Standards in Haematology Guidelines on Diagnosis and Management of Genetic Haemochromatosis. Darwin Medical Communications PTY 2000. Available at www.bcshguidelines.com/pdf/chpt9B.pdf
Guyader D et al, Non invasive prediction of fibrosis in C282Y homozygous haemochromatosis. Gastroenterology 1998; 115: 929 - 36.
Linidi J et al, Evaluation of abnormal liver function tests. Postgraduate medical journal 2003; 79:307-312
Morrison D et al, Serum ferritin level predicts advanced hepatic fibrosis among U.S. patients with phenotypixc haemochromatosis. Annals of Internal Medicine 2003; 138: 627 – 633
Alustixa et al. MR Quantification of Hepatic Iron Concentration. Radiology 2004; 230: 479 - 484
Pietrangelo A, Hereditary Haemochromatosis-A New Look at an Old Disease. Journal of Medicine 2004: 350(23): p2383-2397