Primary haemochromatosis is an autosomal recessive disorder which results in increased intestinal absorption of iron leading to accumulation of iron and its deposition in multiple organs.
The commonest mutation is of the HFA gene, specifically the mutation C282Y.
Patients are now most commonly diagnosed by an incidental finding/biochemically. The classical presentation however was lethargy, arthralgia and (in males) impotence.
Diagnosis tends to be in the 4th decade.
Clinical manifestations of haemochromatosis may be split into those which are reversible and those which are not:
- Reversible manifestations
- Bronzing of the skin (melanin deposition)
- Grey pigmentation of the skin (iron deposition)
- Cardiomyopathy
- Hepatomegaly
- Irreversible manifestations:
- Cirrhosis
- Hepatocellular carcinoma
- Hypopituitism
- Hypothyroidism
- Diabetes mellitus
- Athropathy
- pseudogout
Investigations
- Serum transferrin saturation is best initial screening test - >45% suggests haemochromatosis
- Raised serum ferritin is a sensitive but not specific investigation (as an acute phase protein it will also be raised in infection/inflammation)
- HFE mutation analysis (genetic testing) if transferrin saturation or serum ferritin is abnormal and haemochromatosis is suspected
- Liver biopsy is now only indicated if ferritin >1000 or LFTs abnormal. The classic stain used is Perls stain (blue in colour)
- risks of liver biopsy: bleeding 1-6%; mortality 1 in 10,000.
Treatment
- Regular venesection
- Possibly chelation with deferoxamine or deferasirox
Secondary haemochromatosis is almost always due to an hereditary or acquired disorder of erythropoiesis.
Causes include:
- Thalasseamia
- Sickle cell anaemia
- Hereditary spherocytosis
- Myelofibrosis
Treatment is with chelation.
