Diagnosis of hemochromatosis

The diagnosis is made based on reported symptoms, an investigation of medical family history and the extent of bodily iron overload. The following examinations should be carried out:

1. Transferrin saturation
In the blood, iron binds with a carrier protein and is transported. The carrier protein is called transferrin. One transferrin can carry two molecules of iron. Transferrin saturation indicates to which extent transferrin is loaded with iron. The more iron is absorbed, the more transferrin is saturated with iron. If transferrin in men and woman is loaded with iron by more than 60%, there is most probably an increased iron absorption caused genetically (except type 4A). Young hereditary hemochromatosis patients in particular can have high transferring saturation although the iron storage protein (=ferritin, compare with below) is normal. It has to be taken into consideration that transferrin saturation is dependent on diet and can vary daily.

2. Serum ferritin
Iron is bound with a storage protein in tissue. This protein is called ferritin. The level of ferritin in the blood reflects the amount of iron being stored in tissue. Ferritin values of above 300µg/l in men and 200µg/l in women count as high. It should be noted that ferritin is also increased raises in illnesses that include inflammation. In this case the ferritin value is not reliable for determining levels of stored iron.

3. Genetic mutation
The following analyses are limited to the genetic mutation applicable to the most common hemochromatosise type, the HFE gene mutation of type. For the gene mutations pertaining to types 2 to 4 genetic testing is not carried out. For further information about this please contact us.

Today, two mutations of the HFE gene can be detected in the blood: mutations C282Y and H63D. in the presence of symptoms, a family history and/or high iron values the HFE mutation should be determined. The following gene mutation variations can appear:

C282Y homozygot (C282Y/C282Y): high iron levels combined with C282Y homozygote confirms the diagnosis. In the absence of high iron values (transferrin saturation and ferritin normal) but C282Y homozygote, then there is an asymptomatic mutation, that is, despite the gene mutation there is no iron overload. It is estimated that only about 50% of patients with the mutation absorb too much iron.

C282Y heterozygot-H63D heterozygot (=Compound Heterozygotie): usually iron overload is less pronounced in these patients, and often there are no symptoms. The majority of patients with this mutation do not absorb too much iron.

C282Y heterozygot-H63D wildtyp (wildtyp=keine Mutation): this variation means that the patient carries the C282Y mutation, that is he is healthy and has no disposition toward iron overload. Being a carrier becomes relevant when planning a family, as circa 10% of the Swiss population is a carrier and therefore there is a not insignificant risk that someone’s partner is also a carrier. Is this is the case, there is a 25% chance that the child is homozygote for the C282Y mutation and has a potential disposition towards iron overload.

Other HFE gene mutation variations:

H63D homozygot : this mutation occurs very rarely, but can occasionally lead to an increased absorption of iron and a light form of hemochromatosis.

C282Y wildtyp-H63D heterozygot und C282Y wildtyp-H63D wildtyp: neither of these mutations causes iron overload and therefore hemochromatosis.

4. Liver biopsy
In the past an extraction of liver tissue through biopsy was required for the diagnosis of hemochromatosis, to ascertian the microscopic and chemical presence of iron in the liver. Since the discovery of the HFE gene mutations a liver biopsy has been rendered largely unnecessary for diagnostic purposes. However, patients with hereditary hemochromatosis who have ferritin values above 1000µg/l and abnormal liver values should have a liver biopsy to determine the degree of liver damage and scarring and detecting possibility of a resulting cirrhosis. In this case the liver biopsy is not reccomended on diagnostic grounds but on prognostic ones, as patients with scarring liver deterioration need to be monitored closely medically (cf. below). Patients without genetic mutation and a tendency to iron overload should carry out a liver biopsy for diagnostic purposes.

5. Further blood analyses:
Patients with hereditary hemochromatosis normally have increased liver values (mostly an isolated alanine aminotransferase increase). Sugar in the blood should also be measured, as the pancreas can be damaged by the high iron content, possibly resulting in diabetes. Other blood analyses should be carried out depending on symptoms (e.g. hormonal analysis in the case of erectile dysfunction).

6. Magnetic resonance:
If there is uncertainty about the diagnosis of iron overload and a liver biopsy is not possible on medical grounds then a magnetic resonance tomography can be performed. Normally organs with iron overload will show up as black.