Transferrin Saturation (TS) and Ferritin
Non-fasting test initially if considering the diagnosis and/or as part of a general screen. Both TS and ferritin are required as patients in the early stages of clinical disease can have normal ferritin, but raised TS. In addition, ferritin is an acute phase protein which can be raised in intercurrent illness. If the TS is >50% a fasting TS and ferritin is needed as it avoids effect of diet and diurnal variation.
If the fasting TS is >55% (in men or post menopausal women) or >50% in premenopausal women, this indicates a need for HFE genetic testing, regardless of the ferritin level. These tests may need to be done on a serial basis if the genetic test reveals someone has two susceptibility mutations.
HFE Genetic Testing
A serum ferritin >300mcg/l in men and postmenopausal women or >200mcg/l in premenopausal women, suggests that the patient may be iron overloaded. This should prompt a fasting TS. If this is abnormal (see above) HFE genetic testing should be done and a referral to the liver centre once the genetic test result is available. If the patient is negative for the HFE mutations, further investigations will be needed.
A ferritin of 1000mcg/l should prompt a fasting TS. If this is abnormal, a referral to gastroenterology should be made at the same time as the blood is sent for genetic testing. Genetic testing for HFE mutations is positive in over 95% of those affected in our population. A genetic test never needs to be repeated.
Secondary care will consider the need for liver biopsy and advanced genetic testing.
A liver biopsy will not be needed if the patient:
- is aged <40 yr
- does not have hepatomegaly
- has a normal alanine aminotransferase test (ALT)
- has ferritin <1000mcg/l