Metabolic liver disease: Hemochromatosis Flashcards
Definition
Hereditary haemochromatosis describes an autosomal recessive defect in iron absorption due to a mutation in the HFE gene on chromosome 6, resulting in iron overload.
Epidemiology
Middle age: most commonly presents at 40-50 years old
Male gender: women present later than men due to menstrual iron loss
White
Risk factors
Family history
History of chronic transfusion: only relevant in acquired haemochromatosis, for example in patients with thalassaemia
Aetiology
Missense mutation in haemochromatosis gene (HFE)
- C282Y
- H63D
Acquired haemochromatosis =
- usually occurs due to frequent transfusions of red blood cells
- excessive intake of iron.
Pathophysiology
Unregulated absorption of iron from the gut resulting in iron overload. Iron deposition in multiple tissues and organs leads to disruption of function, most commonly affecting the liver, pancreas, and heart.
Signs
Skin hyperpigmentation: ‘bronze skin’
Arthritic joints
Testicular atrophy
Features of chronic liver disease: e.g. hepatomegaly
Features of congestive cardiac failure: e.g. peripheral oedema due to dilated cardiomyopathy
Symptoms
Usually asymptomatic, especially in the early stages
Vague, non-specific symptoms:
- Early symptoms: lethargy, arthralgia (often of the hands) and erectile dysfunction
- Loss of libido: hypogonadism due to cirrhosis and pituitary dysfunction
- Polyuria and polydipsia: T2DM
Diagnosis
FIRST LINE = Bloods
- Serum transferrin saturation: High
- Serum ferritin: High
- Serum iron: High
- LFTs: deranged
- HbA1c: elevated due to damage to pancreatic beta cells
- Initial screening: requires FBC, transferrin saturation, serum ferritin + serum iron
GOLD STANDARD: Genetic testing
Liver biopsy with pearl stain = Parenchymal cells
Treatment
FIRST LINE = Phlebotomy
- CI = iron chelating agents = desferrioxamine
Family screening
CLASSIC TRIAD
Bronze (slate grey skin)
Hepatomegaly
T2DM
