• HFE gene
• Excess iron absorption. >20g (normal <6g).
• accumulation causes oxidation, damage to hepatocytes, spleen and pancreas.
• Cirrhosis, diabetes & skin pigmentation (bronze) .
• saturated transferrin - haemachromatosis
• gene studies second line diagnosis
• iron deposition in hepatocytes promotes insulin resistance

Demographics

• 40-60y, M=F but men present earlier (due to menstruation)
• More common in Celtic/northern European descendants

Risk factors

FHx - inherit mutated HFR gene

Pathophys:

• HFE gene mutation inhibits hepsidin production, allowing unregulated iron uptake from duodenum and jejunum into plasma. Stored as ferritin. transferrin saturated. binding capacity decreased (because there's so much iron, not many available sites)

• transferrin receptors in areas which complications present: liver, heart, joints, skin, pancreas

• Can also be acquired from ineffective erythropoiesis, dietary overload or parenteral overload