Haemochromatosis (CH) Flashcards
Define haemochromatosis.
Autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation + increased iron release from macrophages
Which groups does haemochromatosis happen more commonly in? (2)
- M>F
- > 40 years of age
What is primary vs secondary haemochromatosis?
- primary haemochromatosis: hereditary, most common form
- autosomal recessive inheritance
- mutations in HFE gene on chromosome 6
- secondary haemochromatosis: caused by iron overload
- commonly transfusion-related
What are the four types of haemochromatosis?
- type 1: hereditary haemochromatosis - most common, autosomal recessive, HFE mutation - arthropathy, skin pigmentation, liver damage, DM, endocrine dysfunction, cardiomyopathy, hypogonadism
- type 2: juvenile - autosomal recessive disorder due to mutation of haemojuvelin gene or hepcidin gene, early onset (<30), hypogonadism and cardiomyopathy prevalent
- type 3: transferrin receptor 2 haemochromatosis - autosomal recessive disorder due to mutation in transferrin receptor 2 gene (7q22), same features as type 1
- type 4: ferroportin disease - autosomal dominant disorder due to mutation of SLC4oA1 gene –> type 4A (loss of function for ferroportin excretion, characterised by iron deposition in spleen) and type 4B (non-classical disease, gain of function, associated with fatigue and joint pain)
What is the phenotypic hallmark of haemochromatosis?
Elevated transferrin saturation - diagnosis confirmed by genetic testing
What is Wilson’s disease (haemochromatosis)?
Autosomal recessive disorder, which leads to excess copper deposition in tissues, hence low serum copper
What combination of two diseases points towards Wilson’s disease (haemochromatosis)?
- liver disease - hepatitis, cirrhosis
- neurological disease - basal ganglia degeneration, asterixis, chorea, dementia
What sign would you see in the eyes of a patient with Wilson’s disease (haemochromatosis)?
Kayser-Fleischer rings –> green-brown rings in the periphery of the iris
What are the blood findings of Wilson’s disease (haemochromatosis)? (2)
- low copper
- low caeruloplasmin
How do we treat Wilson’s disease (haemochromatosis)?
Penicillamine
What is the triad of features in haemochromatosis?
Fatigue, arthralgia (often of the hands) and erectile dysfunction (loss of libido due to hypogonadism)
What are the clinical features of haemochromatosis? (5)
- fatigue, weakness, lethargy
- arthralgia (often of the hands)
- erectile dysfunction (loss of libido due to hypogonadism) + loss of libido
- diabetes mellitus - polyuria, polydipsia, nocturia
- liver issues - cirrhosis, hepatomegaly
What might you see on examination of haemochromatosis? (5)
- hepatomegaly
- skin pigmentation (bronzing to grey/brown with slate-grey patches)
- congestive heart failure
- arrhythmias
- porphyria cutanea tarda - skin disease and liver dysfunction (mildly elevated LFTs) - fragile skin, blisters, bullae
What are some risk factors for haemochromatosis? (5)
- male sex
- middle age
- white ancestry
- Fx
- supplemental iron / high dietary iron intake
What are the first-line investigations for haemochromatosis? (5)
Iron studies:
- serum transferrin saturation (raised)
- serum transferrin (low)
- serum ferritin (raised)
- serum iron (raised)
- total iron binding capacity (low) - capacity of blood to bind to iron
What is the most useful marker of haemochromatosis?
Serum transferrin saturation:
- > 50% in men
- > 45% in women
- low transferrin
What is transferrin and what does it mean if it is high or low (haemochromatosis)?
Iron carrier protein:
- high in IDA
- low in iron overload
What is transferrin saturation and what does it mean if it is high or low (haemochromatosis)?
Percentage of transferrin (iron carrier) bound to iron:
- high suggests iron overload
- low suggests IDA
What is serum ferritin like in haemochromatosis?
Raised:
- > 674picomols/L (>300ng/L) in men
- > 449picomols/L (>200ng/L) in women
How can we confirm diagnosis of haemochromatosis?
Genetic testing - if there is a first-degree relative with haemochromatosis and confirmed iron overload, it will show mutation of HFE gene
What finding increases likelihood of severe clinical complications in haemochromatosis?
Serum ferritin >1000ug/L
What are some differential diagnoses for haemochromatosis? (6)
- iron overload from chronic transfusion
- hepatitis B or C
- NAFLD
- dysmetabolic hyperferritinaemia
- excessive iron supplementation
- hereditary aceruloplasminaemia
What is required for diagnosis of haemochromatosis?
282Y homozygosity required
What are the stages of haemochromatosis? (5)
- stage 0: normal serum transferrin and ferritin + no clinical Sx
- stage 1: increased transferrin saturation (>45%), normal ferritin + no clinical Sx
- stage 2: increased transferrin saturation + increased serum ferritin (>300ng/L men, >200ng/L women) + no clinical Sx
- stage 3: increased transferrin saturation + increased serum ferritin + clinical Sx affecting QoL attributed to this disease (e.g. asthenia, impotence, arthropathy)
- stage 4: increased transferrin saturation + increased serum ferritin + clinical Sx manifesting organ damage predisposing to early death (e.g. cirrhosis with risk of HCC, insulin-dependent DM, cardiomyopathy)
What dietary changes are needed in haemochromatosis management?
Diet low in iron
Avoid iron/vitamin C supplements + alcohol
What is the first-line management for haemochromatosis?
Therapeutic phlebotomy (regular venesection) - monitor via ferritin levels and transferrin saturation
What is the second-line treatment for haemochromatosis?
If therapeutic phlebotomy cannot be performed (venesection not possible) –> drug-induced iron chelation (deferoxamine) to lower iron levels
How do we manage stage 0 haemochromatosis?
- observation
- 3-yearly follow up
- avoid iron/vitamin C supplements
- avoid alcohol
- hep A and B vaccination
How do we manage stage 1 haemochromatosis (raised transferrin saturation)?
1-yearly follow up
How do we manage stages 2-4 haemochromatosis (high ferritin +/- clinical symptoms)?
- therapeutic phlebotomy or erythrocytapheresis
- 7ml/kg of body weight per session but <550ml
- monitor ferritin and transferrin saturations
- check Hb and MCV for anaemia
- iron chelation therapy (deferasirox/desferrioxamine/deferiprone/deferoxamine) - if phlebotomy CI, severe heart disease, problems with venous access
What are some complications of haemochromatosis? (8)
- hepatocellular carcinoma (may need US screening)
- liver cirrhosis
- DM
- chronic CHF - dilated RCM
- AF
- hypogonadism
- bone loss
- infections
