Assessment of hereditary haemochromatosis

In 90% of patients with an elevated serum ferritin, a condition other than iron overload is the cause; for example, chronic alcohol consumption, obesity, diabetes, liver disease, malignancy, infection or inflammation. An elevated serum ferritin with a fasting serum transferrin saturation of 45% or more may indicate iron overload.

The Australian Red Cross Lifeblood High Ferritin App includes a calculator that can be used to identify potential causes of hyperferritinaemia other than hereditary haemochromatosis, based on a person’s ferritin, body mass index (BMI) and alanine aminotransferase (ALT) concentration.

HFE gene mutation analysis is used to confirm the diagnosis of haemochromatosis. Three specific mutations of the HFE gene (C282Y, H63D, S65C) are commonly reported, but only C282Y homozygotes and occasional C282Y/H63D compound heterozygotes develop clinically significant iron overload. The risk of iron overload and prevalence of each genotype is shown in HFE gene mutations and risk of iron overload. Disease penetrance is low (20 to 30%), even in C282Y homozygotes, and may depend on other factors such as the sex of the patient, alcohol consumption and steatosis. Around 1 in 7 people have one abnormal HFE gene; they will not develop haemochromatosis.

Screen the first-degree relatives of patients with haemochromatosis (ie C282Y homozygotes) using HFE gene mutation analysis and iron studies. Screening of the patient’s partner is useful to assess the risk of hereditary haemochromatosis in their children.

If hereditary haemochromatosis has been excluded in a patient with elevated serum ferritin, assess for other potential causes and refer to a specialist if necessary. For these patients:

• if serum ferritin is more than 1000 micrograms/L, refer to a specialist with expertise in iron overload
• if serum ferritin is 1000 micrograms/L or less, address reversible causes and repeat iron studies
• encourage voluntary blood donation.