Investigations

In the UK, the British Society of Haematology Guidelines (Fitzsimmons et al, 2018) represent best practice in the diagnosis and care of people with genetic haemochromatosis.

There are two main blood tests that should be carried out if a person presents with two or more of the above-mentioned symptoms:

• Serum Ferritin (SF): A measurement of the protein ferritin circulating in the blood serum. SF correlates well with iron storage. However, a normal ferritin does not rule out a diagnosis of GH. For every 1 mcg/l in the SF level it is estimated that about 10 mg of iron is stored in the body. SF can be within normal limits and 1000s above normal range in a patient with GH, therefore Transferrin Saturation measurements are also important for a differential diagnosis.

Please note: SF is an acute phase reactant and can be raised in other inflammatory conditions, metabolic syndrome, and alcohol consumption.

 

• Transferrin Saturation (TS): is a measurement of the amount of iron that transferrin can bind and transport in the serum. It is a glycoprotein produced in the liver, and both it and its serum levels are regulated by the iron that is stored in the body. It decreases when iron levels are low and increases when iron levels are high.

 

Normal range of iron and transferrin saturation
	Males	Females
Serum Ferritin (mcg/l)	15 - 300	15 – 200 15 – 300 (postmenopausal)
Transferrin saturation (%)	16 – 50	16 – 45

Table 3: Normal ranges of ferritin and transferrin saturation

 

• Liver Function Tests (LFT’s) and Full Blood Count (FBC) should be checked to rule out other problems and liver damage. If LFT’s are abnormal then a liver ultrasound scan (USS) should be arranged as well as further blood investigations and referral to secondary care

 

• Genetic Testing: When SF and TS are abnormal, genetic testing should be undertaken either within primary care or after referral to secondary care. NHS England includes two tests in the National Genomic Test Directory - R95 and R96. Testing for the C282Y and H63D mutation is a simple and cheap test (R95). Rarer mutations may need further genetic testing (R96). Two copies of the C282Y mutation combined with iron overload gives a confident diagnosis GH. If someone has one copy of the gene and has iron overload, then further genetic testing needs to be undertaken. A SF of over 1000 mcg/l and /or abnormal liver function tests requires urgent referral to a secondary care to exclude liver damage.
• Genetic counselling should also be offered if available.
• Magnetic Resonance Imaging (MRI) and USS can show if there have been areas of iron overload and/or liver cirrhosis.

 

Learning points

• Serum Ferritin is an acute phase reactant and can be raised in other inflammatory conditions, metabolic syndrome, and alcohol consumption.
• Transferrin Saturation (TS) is a measurement of the amount of iron that transferrin can bind and transport in the blood serum. When iron levels high within the body, transferrin saturation will also be high.
• If liver function tests are abnormal, then USS scan of the liver should be arranged and referral to secondary care should be considered.
• HFE gene test should be checked if SF and TS are abnormal
• A patient diagnosed with GH, their 1^st degree family members should be offered genetic screening

Next steps

Treatment