Haemochromatosis Flashcards
What is haemochromatosis?
multisystem disorder of dysregulated dietary iron absorption and increased iron release from macrophage
What sort of genetic syndrome is haemochromatosis?
autosomal recessive disorder
What gene and mutations are responsible for haemochromatosis?
HFE gene and 2 commonest mutations: C282Y AND H63D
What is typical epid for haemochromatosis?
- male
- northern european
- middle age
What are RF for haemochromatosis?
- Male gender
- Middle age
- Positive family history
- High dietary iron intake
- White ancestry
What are the symptoms of haemochromatosis?
- Fatigue
- Weakness
- Lethargy
- Athralgias
- Hepatomegaly
- DM
- Impotence in males
- Loss of libido
- Skin pigmentation
What are the possible differential diagnosis of haemochromatosis?
- Iron overload from chronic transfusion
- Hepatitis B
- Hepatitis C
- Non-alcoholic fatty liver disease (NAFLD)
- Dysmetabolic hyperferritinaemia
- Excessive iron supplementation
- Hereditary aceruloplasminaemia
What the 1st line investigation for haemochromatosis?
- Serum transferrin
2. Serum ferritin
What would serum transferrin saturation be like in haemochromatosis?
> 45%
What would serum ferritin be like in haemochromatosis?
: raised; >674 picomols/L (>300 nanograms/mL) in men; >449 picomols/L (>200 nanograms/mL) in women
What other investigations would you consider for haemochromatosis?
- HFE mutation analysis
- MRI liver: liver to muscle signal intensity <0.88
- Liver biopsy: iron content raised (PERL’S STAIN)
- LFTs: aminotransferase levels above normal
- Fasting BS: raised
- ECHO: mixed dilated-restrictive or dilated cardiomyopathy
- ECG : decreased QRS amplitude and T-wave flattening or inversion
- Test, FSH, LH: lower than normal levels
- Bone densitometry: osteopenia (T score
What is stage 0 disease?
C282Y homozygosity with normal serum transferrin saturation and ferritin, and no clinical symptoms
What is the 1st line treatment for stage 0 disease?
1st line: observation and 3 yearly follow up
Plus: lifestyle modifications
Adjunct: Hep A + B vaccine
What is stage 1 disease?
C282Y homozygosity with increased transferrin saturation (>45%), normal ferritin, and no clinical symptoms
What is the 1st line treatment for stage 1 disease?
1st line: Observation and 1 yearly follow up
Plus: lifestyle modifications
Adjunct: Hep A and B vaccine
What is the 1st line treatment for stage 2,3,4 disease?
1st line: phlebotomy regime – venesection until ferritin is <50mcg/L
Plus: lifestyle modifications
Adjunct: Hep A and B vaccine
What is the 2nd line treatment for stage 2,3,4 disease?
2nd line: iron chelation therapy
Plus lifestyle modifications
Adjunct: hep A and B vaccine
What are the possible complications of haemochromatosis?
- Cirrhosis
- DM
- Chronic congestive heart failure
- Hepatocellular carcinoma
- Hypogonadism
- Bonne loss
- Infections
What is the prognosis for haemochromatosis?
VENESECTION RETURN LIFE EXPECTANCY TO NORMAL IF NON DM AND NON CIRRHOTIC
What is a primary haemochromatosis?
(AR inherited) due to mutation of HFE gene on Chr 6
What is secondary haemochromatosis?
due to frequent blood transfusions, iron supplementation or diseases of erythropoiesis
What is the epid for haemochromatosis?
- More common in middle aged males
2. Females present later
What are the molecules involved in iron transport?
- transferrin
- hepcidin
- ferroportin
What is the main function of transferrin?
- to deliver iron to where it is needed
- via the plasma
- holds iron in an inert state whilst it travels through the blood
What is the function of ferroportin?
portal for iron to travel from the intestine into the blood
What is hepicidin?
APP which essentially destroys ferroportin seeking to inhibit iron absorption in the blood (physiological regulation)
What is the patho of herediatary/primary haemochromatosis?
- a defect in the HFE gene means that transferrin binds poorly to its receptor
- causing the liver to reduce hepcidin production
What is the result of the reduced hepicidin production?
- ferroportin activity in the enterocytes is unregulated
- so more iron is transported across the enterocytes
- this results in iron accumulation and damage to the affected organs.
Why do females present later in haemochromatosis?
as they have an additional method of excreting iron through menstruation, whereas this is not possible in males so iron accumulates more quickly
What are the commonly affected organs in haemochromatosis?
- liver
- pancreas
- skin
- pituitary
- heart
- joints
What is the classic triad for haemochromatosis?
- cirrhosis
- diabetes
- bronze pigmentation
What are the common non-specific symptoms of haemochromatosis?
- lethargy
- impotence
- arthralgia
What are the symptoms relating to haemochromatosis?
- deranged LFTs
2. diabetes mellitus
What is haemochromatosis?
multisystem disorder causing multi organ dysfunction due to iron deposition and its toxicity to cells
What bloods are done and the result for haemochromatosis?
- Serum ferritin raised
- Transferrin sat >45%
- LFTs raised AST and ALT
- FBC normal
What genetic testing is done for haemochromatosis?
C282Y mutation of HFE gene
What other Ix are done for haemorhcromatosis?
- Liver biopsy
* Further Ix guided by the PC
When are Ix done?
clinical features of haemochromatosis OR for 1st degree relatives of hereditary haemochromatosis patients
What does serum ferritin show?
APP that acts as a store of iron – it indicates the level of iron stores in the body
Why are transferrin sats so high for haemochromatosis?
- more iron
2. less transferrin due to defective gene
When are LFTs indicated in haemochromatosis?
if there is iron deposition causing hepatocyte toxicity
Why do you do FBC with haemochromatosis?
important to ensure you rule out other causes of fatigue and lethargy such as IDA
What other Ix may be done for haemochromatosis?
- fasting blood sugars
- ECG/echo
- serum gonadotrophin levels
What is management guided by?
- serum transferrin saturation
- ferritin
- clinical symptoms
What lifestyle changes are advised for haemochromatosis?
on avoiding exogenous iron and vitamin C supplements, limiting alcohol intake
What is stage 0 haemochromatosis?
normal iron labs with no clinical symptoms
What is the management for stage 0 haemochromatosis?
monitoring iron labs and symptoms every 3 years
What is stage 1 haemochromatosis?
transferring sats>45%, normal ferritin, no symptoms
What is management for stage 1 haemochromatosis?
monitoring iron labs and symptoms every 1 year
What is stage 2-4 haemochromatosis?
Transferrin sats>45%, raised ferritin, +/- clinical symptoms
What is stage 2-4 haemochromatosis management?
venesection/iron chelation therpay
What is end stage liver disease?
features of chronic liver failure and cirrhosis
What is the management for end stage liver disease?
liver transplant
What is Phlebotomy treatment?
- Phlebotomy , or venesection, is the process by which blood is removed from the patient
- to stimulate haematopoiesis,
- utilising some of the excess iron for haem synthesis
When is iron chelation therapy indicated for?
stage 2, 3 or 4 patients for whom phlebotomy is contraindicated (such as anaemia, cardiac disease or venous access issues)
When is iron chelation therapy contraindicated?
- anaemia
- cardiac disease
- venous access issues
What are patient outcomes for transplantation for haemochromatosis?
- patients with end-stage cirrhotic liver disease due to haemochromatosis are candidates for liver transplantation
- important to note that transplant outcomes are worse compared to other causes of cirrhosis
