Epidemiology
- Age of onset: individuals > 40 years
- Symptoms start to show when body iron levels reach > 20 g.
- Before menopause, women lose iron via menstruation and pregnancy, which slows down iron accumulation within the body. As a result, symptom onset occurs later in women (typically postmenopausal) than in men.
Etiology
Pathophysiology
HFE gene defect (homozygous) → defective binding of transferrin to its receptor → ↓ hepcidin synthesis by the liver → unregulated ferroportin activity in enterocytes → ↑ intestinal iron absorption → iron accumulation throughout the body → damage to the affected organs
Tip
Don’t mess up with Wilson disease
Clinical features
- Liver
- Abdominal pain
- Hepatomegaly
- Cirrhosis
- Increased risk of hepatocellular carcinoma (common cause of death)
- Pancreas: signs of diabetes mellitus (polydipsia, polyuria)
- Skin: hyperpigmentation, bronze skin
- Pituitary gland: hypogonadism, erectile dysfunction, testicular atrophy, loss of libido, amenorrhea
- Joints: arthralgia (typically symmetrical arthropathy of the MCP joints II and III), chondrocalcinosis (accumulation of calcium pyrophosphate)
- Heart
- Early: diastolic left ventricular dysfunction (restrictive pattern)
- Later: cardiac remodeling & dilated cardiomyopathy
Tip
Classic triad of cirrhosis, diabetes mellitus, skin pigmentation (“bronze diabetes”).
Diagnostics
- Liver biopsy
- Hemosiderin (normally golden yellow on microscopy) appears blue with the Prussian blue stain.
- Pattern of hereditary hemochromatosis: pronounced parenchymal siderosis (accumulation of hemosiderin within the tissue) in hepatocytes and bile duct epithelium
- Pattern of secondary iron overload: Kupffer cells (specialized macrophages) containing hemosiderin
Treatment
Iron chelation therapy
- First-line treatment for secondary iron overload due to iron-loading anemia
- Chelating agents: deferoxamine