Haemochromatosis

Question 1

Define haemochromatosis

Answer 1

•  Haemochromatosis = iron overload
• Autosomal recessive multisystem disorder
• Dysregulated iron absorption in the intestines and increased iron release from macrophages.
• Iron deposition in, heart, joints, kidney, liver, spleen, pituitary, pancreas and adrenals.

Question 2

What are the causes/risk factors of haemochromatosis?

Answer 2

• Hereditary Haemochromatosis, HH:

• Type 1 HFE: Mutation of the HFE gene on Chromosome 6p - most common causative mutation is C282Y (85-90% of HH)
• Type 2A Juvenile HJV (Haemojuvelin) gene mutation
• Type 2B Juvenile HAMP (Hepcidin Antimicrobial Peptide) gene mutation
• Type 3 TFR2 (Transferrin Receptor 2) gene mutation
• Type 4 Ferroportin –SLC40A1 gene mutation.
• HH is an autosomal recessive (type 4 –Ferroportin –which is autosomal dominant).

• Secondary Haemochromatosis:

• Severe chronic haemolysis
• Multiple blood transfusions
• Excess dietary iron (very rare)
• Excessive iron supplements –especially parenteral supplements

Rusk factors: 
• Middle age
• Male
• White ancestry
• Family History
• Supplemental iron

Question 3

What are the symptoms of haemochromatosis?

Answer 3

Non-specific symptoms:
• weakness
• fatigue
• abdominal pain

EARLY symptoms are vague: 
• Fatigue  
• Weakness  
• Arthropathy 
• Erectile dysfunction  
• Heart problems  
• May be an incidental finding (e.g. LFTs, serum ferritin)  

Later features:
• Small/Large joint pain (especially 2nd/ 3rd MCPJ)
• Liver disease symptoms (e.g. jaundice, petechiae and bruising).
• DM: polyuria, nocturia, thirst.
• Hypogonadism
• HF: dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea.

LATE symptoms: 
EARLY symptoms are vague: 
• Diabetes mellitus  
• Bronzed skin  
• Hepatomegaly 
• Amenorrhoea 
• Hypogonadism  - impotence, loss of libido  
• Cirrhosis  
• Cardiac - arrhythmias and cardiomyopathy  
• Neurological and psychiatric problems

Question 4

What are the signs of haemochromatosis?

Answer 4

• Normal examination in earlier stages. Then signs categorised as SH-LH: 
• Skin - Slate-grey pigmentation due to increased melanin deposition
• Heart - Signs of HF 
• Liver - Hepatosplenomegaly 
• Hypogonadism: 
- Gynaecomastia 
- Loss of hair 
- Testicular atrophy

Question 5

What investigations are carried out for haemochromatosis?

Answer 5

• Serum Iron - raised
• Serum Iron - raised
• Serum Ferritin - raised (>674 picomols/ in men; >449 picomols/L in women)
• Serum Transferrin - AKA TIBC, Low
• Transferrin Saturation - raised >45%
• HFE Gene Mutation - Positive in type 1 HFE.

Liver Complications:
•  LFTs 
• Coagulation Screen 
• Liver Biopsy –iron visualised by the Perls’ stain 
• MRI for Fe Loading 

Pancreas Complications:
• Blood glucose (fasting or random) for DM.

Pituitary Function:
• Low Testosterone 
• Low or inappropriately normal FSH/LH 
• TFTs 
• IGF-1 
• Cortisol 

Heart Complications:
• ECG and Echo

Joint Complications:
• Joint X-ray –linear calcification due to iron deposition

Bone complications:
• DEXA –osteopaenia