What are the laboratory tests for hereditary hemochromatosis (HH)?

From the Guidelines

The initial step in testing for hemochromatosis should include the assessment of serum iron parameters, specifically transferrin saturation and serum ferritin, as recommended by the most recent guidelines 1. The diagnosis of hemochromatosis involves a combination of clinical evaluation, laboratory tests, and genetic analysis.

Key Laboratory Tests

• Transferrin saturation: This test measures the percentage of transferrin that is saturated with iron. Elevated levels (>45%) can indicate iron overload 1.
• Serum ferritin: This test measures the level of ferritin in the blood, which can indicate iron storage. Elevated levels can suggest hemochromatosis, but it's essential to consider other conditions that may cause elevated ferritin, such as inflammation or liver disease 1.

Additional Testing

• Genetic testing for HFE gene mutations: If transferrin saturation and serum ferritin are elevated, genetic testing should be performed to identify mutations associated with hereditary hemochromatosis, particularly C282Y and H63D mutations 1.
• Complete blood count, comprehensive metabolic panel, and hemoglobin A1C: These tests can help assess for complications and associated conditions, such as liver disease, diabetes, and cardiovascular disease.

Special Considerations

• First-degree relatives of affected individuals should be screened for hemochromatosis, as the disease has an autosomal recessive inheritance pattern 1.
• Regular monitoring of ferritin levels is necessary for diagnosed patients to guide treatment frequency and assess response to therapy.
• Testing should be performed in a fasting state for accurate transferrin saturation results, although fasting does not improve diagnostic utility 1.

Clinical Evaluation

• Patients with clinical and biochemical signs of hemochromatosis, elevated transferrin saturation, and high serum ferritin concentrations should be genetically tested for hemochromatosis after informed consent for genetic testing has been obtained 1.
• Individuals with increased liver iron evident on liver biopsy or MRI should be clinically assessed and biochemically tested for haemochromatosis (serum ferritin and transferrin saturation) 1.

From the Research

Lab Work for Hemochromatosis

Lab work for hemochromatosis typically involves the following tests:

• Measurement of serum transferrin saturation and serum ferritin level to screen for iron overload 2, 3, 4, 5, 6
• Liver biopsy to confirm the diagnosis, assess iron overload, and detect cirrhosis 2, 3, 5
• HFE gene testing to detect genetic mutations associated with hemochromatosis, particularly in family members of affected individuals 2, 4, 6
• Magnetic resonance imaging (MRI) scan to support the diagnosis and detect iron overload 3
• Phlebotomy to reduce iron stores and prevent complications 2, 3, 6

Diagnostic Criteria

The diagnosis of hemochromatosis is suggested by:

• Elevated serum ferritin level and/or transferrin saturation 2, 3, 4, 5, 6
• Characteristic findings on liver biopsy, such as iron overload and cirrhosis 2, 3, 5
• Response to phlebotomy, such as a rapid return to normal hematocrit levels 3

Screening and Case Detection

Screening for hemochromatosis is recommended:

• In family members of affected individuals 2, 4
• In high-risk groups, such as patients with clinical manifestations consistent with the diagnosis 4
• In patients with elevated iron indices and a suspicion for hemochromatosis or liver disease 6