Hemochromatosis
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
- Wilson disease is accumulation of copper, and has neurologic symptoms.
Clinical features
Tip
Classic triad of cirrhosis, diabetes mellitus, skin pigmentation (“bronze diabetes”).
- 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)
- Caused by iron deposition in the articular cartilage and synovium
- X-ray findings include characteristic deformities (eg, hook-like osteophytes)
- Heart
- Early: diastolic left ventricular dysfunction (restrictive pattern)
- Later: cardiac remodeling & dilated cardiomyopathy
| Feature | Hemochromatosis | Wilson Disease |
|---|---|---|
| Genetics | Autosomal recessive; HFE gene mutations | Autosomal recessive; ATP7B gene mutations |
| Iron Metabolism | Excessive iron absorption leading to overload | Impaired copper excretion leading to accumulation |
| Common Symptoms | Fatigue, joint pain, diabetes, skin changes | Liver dysfunction, neurological symptoms, Kayser-Fleischer rings |
| Diagnosis | Serum ferritin, liver biopsy, genetic testing | Serum ceruloplasmin, 24-hour urinary copper, liver biopsy |
| Treatment | Phlebotomy, chelation therapy if needed | Chelation therapy (e.g., penicillamine), zinc therapy |
| Complications | Liver cirrhosis, diabetes, heart disease | Liver failure, neurological damage, psychiatric issues |
| Age of Onset | Usually in middle age | Typically in childhood or young adulthood |
| Prevalence | Common in people of Northern European descent | More common in certain populations (e.g., Ashkenazi Jews) |
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
- Hemosiderin (normally golden yellow on microscopy) appears blue with the Prussian blue stain.
Treatment
Iron chelation therapy
- First-line treatment for secondary iron overload due to iron-loading anemia
- Chelating agents: deferoxamine