From the Guidelines
Diagnosing hemochromatosis requires a combination of blood tests, including serum transferrin saturation and serum ferritin levels, as well as genetic testing for the HFE gene mutations, particularly C282Y and H63D, as recommended by the most recent guidelines 1.
Key Diagnostic Criteria
- Serum transferrin saturation (TSAT) greater than 45% and elevated ferritin levels (>200 µg/L in females and >300 µg/L in males and post-menopausal women) suggest iron overload, as indicated by the European Association for the Study of the Liver guidelines 1.
- Genetic testing for the HFE gene mutations, particularly C282Y and H63D, should be performed to confirm hereditary hemochromatosis, with the C282Y homozygous mutation being responsible for most cases of hereditary hemochromatosis.
Diagnostic Approach
- Initial screening should include serum transferrin saturation and serum ferritin levels, with abnormal results prompting further evaluation, including genetic testing and potentially liver biopsy or MRI to quantify hepatic iron concentration and assess for liver damage 1.
- Family members of diagnosed patients should also be screened, as the condition has an autosomal recessive inheritance pattern, highlighting the importance of genetic testing in diagnosis and screening 1.
Importance of Early Diagnosis
- Early diagnosis is crucial as treatment can prevent complications such as liver cirrhosis, diabetes, heart problems, and joint damage, emphasizing the need for prompt and accurate diagnosis 1.
- Regular monitoring of iron levels is essential for diagnosed patients, even if they are asymptomatic, to guide therapeutic phlebotomy needs and prevent organ damage, as recommended by the European Association for the Study of the Liver guidelines 1.
From the Research
Diagnosing Hemochromatosis
Diagnosing hemochromatosis involves a combination of clinical examination, laboratory tests, and genetic testing. The key steps in diagnosing hemochromatosis are:
- Clinical examination to assess for signs and symptoms of iron overload
- Laboratory tests to measure plasma iron parameters, such as serum ferritin, serum iron, and transferrin saturation 2, 3
- Imaging studies to assess for iron accumulation in organs such as the liver and pancreas 2
- Genetic testing to identify mutations in genes associated with hemochromatosis, such as HFE, HAMP, HJV, and TFR2 2, 4
Laboratory Tests
Laboratory tests play a crucial role in diagnosing hemochromatosis. The most commonly used tests include:
- Serum ferritin level, which is the best predictor of body iron stores 5
- Serum iron and transferrin saturation, which can indicate iron overload 3, 4
- Unsaturated iron binding capacity, which can help assess iron stores 5
Genetic Testing
Genetic testing is an important tool in diagnosing hemochromatosis. The most commonly used genetic test is the HFE gene test, which can identify mutations associated with hereditary hemochromatosis 3, 4. However, it is important to note that 5-15% of patients with phenotypic hemochromatosis do not have HFE gene mutations, and therefore, other diagnostic tests such as MRI or liver biopsy may be necessary 4.
Challenges in Diagnosing Hemochromatosis
Diagnosing hemochromatosis can be challenging due to the nonspecific nature of the symptoms and the presence of other conditions that can cause elevated serum ferritin levels, such as acute and chronic liver disease, and systemic inflammatory states 6. Therefore, it is essential to use a combination of clinical examination, laboratory tests, and genetic testing to confirm the diagnosis of hemochromatosis.