Fact-sheet: Hemochromatosis
Updated on 02/14/2025 at 9:28 AM
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Definition
Hemochromatosis is a genetic disease characterized by iron overload in the body.
The term hemochromatosis is reserved for genetic hemochromatosis, while secondary iron overload is referred to as hemosiderosis.
Hereditary hemochromatosis is the most common genetic disease in France, affecting one in 300 individuals.
Clinical features
The clinical signs of hemochromatosis are often subtle, especially at the outset.
Classic symptoms include asthenia, joint pain (particularly of the 2nd and 3rd fingers), melanoderma, hypogonadism, and cardiac disorders.
Joint involvement is a complication that impairs quality of life. In men, the first symptoms appear around 25-35 years of age, whereas in women, they occur later (menopause).
Clinical manifestations depend on the organs affected by the iron overload, notably the liver, pancreas, heart, endocrine glands, skin, and joints.
Laboratory findings
- Increased ferritinemia and transferrin saturation coefficient (> 45%).
- Genetic testing: confirms the diagnosis.
In dysmetabolic hepatosiderosis, hyperferritinemia may be present with a normal saturation coefficient.
Radiography
Radiographic findings of osteoarticular involvement in hemochromatosis may include:
- Axial and/or appendicular bone rarefaction
- Chondrocalcinosis (calcium pyrophosphate dihydrate [CPPD] crystal deposits), with rare para-articular calcifications
- Arthropathy similar to CPPD arthropathy with distinctive features: predilection for the metacarpophalangeal (MCP) joints of the 2nd and 3rd rays, then the 4th and 5th rays
- Multiple microgeodes at the MCP joints
- Multiple subchondral macrogeodes (hips, wrists, etc.)
- Osteophytosis of the radial border of the metacarpal heads
Ultrasound
Marked hepatic iron overload can result in hepatic hyperechogenicity, but this finding is nonspecific.
CT
Before contrast injection, hepatic hyperdensity (>70HU) may be observed, but this finding is nonspecific and poorly sensitive.
The presence of steatosis can mask hepatosiderosis.
Computed Tomography (CT) therefore has no role in this setting.
MRI
Iron causes a marked signal drop due to its paramagnetic effect.
• Signal drop: signal loss proportional to the degree of iron overload. This signal drop is more easily detected with T2* gradient-echo sequences.
• Liver/muscle comparison: To assess the decrease in hepatic signal, it should be compared to muscle signal. Normally, muscle signal is lower than liver signal.
• Quantification: Precise quantification of overload can rely on several methods, notably the liver/muscle ratio and T2 calculation. The liver-muscle comparison method is effective for estimating mild overload but plateaus for major overload exceeding 300 μmol/g.
• Associated lesions:
o Genetic hemochromatosis is not accompanied by splenic overload.
o Pancreatic signal drop is rare and observed in cases of cirrhosis or portal hypertension in genetic hemochromatosis with major overload.
o Cardiac overload should be sought in cases of major hematologic overload.
o Pituitary signal drop is possible in cases of major overload.
• Cirrhosis: Cirrhosis may be suspected based on signs of hepatic dysmorphia, nodularity, or heterogeneity, on the presence of portal hypertension, or on the finding of decreased pancreatic signal on MRI.
• Hepatocellular carcinoma: Detection of a tumor nodule is facilitated by MRI prior to treatment.
Management
In the setting of hyperferritinemia with transferrin saturation > 45%, chronic liver disease, compensated dyserythropoiesis, or genetic hemochromatosis should be considered.
Genetic testing is essential. If genetic testing is negative or if hyperferritinemia is associated with a transferrin saturation below 45%, MRI is useful to quantify hepatic iron content and to look for dysmetabolic iron overload syndrome.
Classification
- Genetic hemochromatosis (type 1, related to an HFE gene mutation)
- Secondary hemochromatoses (hemosiderosis) Chronic liver disease (alcoholic cirrhosis, chronic hepatitis C)
- Hemolytic anemias
- Myelodysplastic syndromes
- Metabolic syndrome
- Hepatic iron overload Mild overload: up to 80 μmol/g
- Moderate overload: up to 150 μmol/g
- Severe overload: up to 300 μmol/g
- Major overload: beyond 300 μmol/g
Differential diagnosis
- Fatty liver
- Other metal overload (copper)
- Calcium pyrophosphate deposition disease (CPPD)
- Amiodarone toxicity
- Hemophilia
- Hemarthrosis
- Rheumatoid arthritis
- Pigmented villonodular synovitis