Ferritin = an intracellular Fe storage protein.
- Serum level = an indirect measure of Fe stores. Normal ranges:
- Men: 20 – 350µg/L
- Women: 10 – 150µg/L
The Ferritin is often ‘falsely’ raised in liver disease and ‘acute phase reactions’ (e.g. chronic infectious/inflammatory conditions – may have raised CRP)
- Consider utilising the haematology or gastroenterology Advice and Guidance (via the NHS eReferral service) for additional guidance on investigations if the patient does not fall into one of the categories below
High Ferritin >350μg/L (NO CONCERN IF BELOW THIS LEVEL)
GP please send: FBC, repeat Ferritin, Transferrin Saturation, CRP, LFTs, gGT ‘HFE gene studies if transferrin saturation raised’.
High Ferritin with Transferrin Saturation (Tfn Satn) <50%, consider
- ‘Acute phase reaction’ (infection, inflammation, neoplasia)
- Liver disease
- Diabetes mellitus, ‘metabolic syndrome’ (less often)
- (Very high Ferritins found in Still’s disease, haemophagocytic syndrome)
- Raised Tfn Satn with homozygosity for C282Y mutation, or compound heterozygosity (for C282Y & H63D mutations) in HFE gene.
Fe overload often exacerbated by EtOH excess, obesity.
- Clinical presentations: fatigue, abnormal LFTs, loss of libido, erectile dysfunction, arthritis (esp of 1st/2nd metacarpo-phalangeal joints of hands, & large joints), diabetes (type 1 or 2), porphyria cutanea tarda, cardiomyopathy, hypothyroidism.
- Refer all C282Y homozygotes and C282Y/H63D compound heterozygotes to Haematology OPD for evaluation & ?phlebotomy.
- Occasionally excess Fe absorption can be controlled by dietary and EtOH restriction, and a PPI rather than long term phlebotomy.
Fe overload (Tfn Satn >50%) without two HFE gene abnormalities
- Refer to Liver OPD – may need liver biopsy to establish degree and clinical significance of iron overload
- 90% of clinical genetic haemochromatosis is due to C282Y and/or H63D in HFE. There are other, much rarer genetic causes, for which testing may be available after clinic evaluation.
- May still require phlebotomy if Fe judged to be toxic to liver etc.
Two HFE gene abnormalities with Ferritin <350μg/L
- ‘Incomplete penetrance’: 70% of C282Y/C282Y and 90% of C282Y/H63D will not develop clinical Fe overload.
- Still needs Haematology OPD evaluation and advice.
- Consider annual Ferritin, especially in young men and post-menopausal women.
- Will be initiated by Haem OPD, but we may request relatives to attend GP for: FBC, Ferritin, transferrin sat, HFE gene studies, LFTs, gGT.
- Test all full siblings.
- If >1 child, consider testing other parent first. Only test children if other parent also has an HFE mutation. Usually only test when >18 yrs old.
- Refer to Haem OPD any person with two HFE mutations.