What are the blood tests to diagnose hereditary hemochromatosis (HH) and Wilson's disease (WD)?

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From the Guidelines

Blood tests for hemochromatosis and Wilson's disease involve specific markers that help diagnose these genetic disorders of metal metabolism. For hemochromatosis, the primary tests include serum ferritin and transferrin saturation, with elevated levels (ferritin >300 ng/mL in men or >200 ng/mL in women, and transferrin saturation >45%) suggesting iron overload, as recommended by the EASL clinical practice guidelines on haemochromatosis 1. Genetic testing for the HFE gene mutations (particularly C282Y and H63D) confirms hereditary hemochromatosis. For Wilson's disease, the essential tests include serum ceruloplasmin (typically low at <20 mg/dL), 24-hour urinary copper excretion (elevated >100 μg/24 hours), and serum free copper levels, as outlined in the diagnosis and treatment of Wilson disease update 1. These tests reflect copper metabolism abnormalities caused by ATP7B gene mutations. Additional blood tests for both conditions include liver function tests to assess organ damage, as both diseases can affect the liver. Complete blood count may also be ordered to evaluate for anemia or other blood cell abnormalities. These tests are crucial for early diagnosis, as both conditions can cause serious organ damage if left untreated, but respond well to interventions like phlebotomy for hemochromatosis or chelation therapy for Wilson's disease. Some key points to consider when interpreting these tests include:

  • Serum ferritin level is not only a marker of iron overload but also an acute phase reactant, tumor marker, and indicator of increased angiogenesis, and its levels can be elevated in conditions associated with fatty liver disease 1.
  • Serum ceruloplasmin concentrations are elevated by acute inflammation and in states associated with hyperestrogenemia, which can affect the interpretation of the results 1.
  • The diagnostic cutoff levels for serum ferritin and transferrin saturation may vary, but generally, levels greater than 200 µg/mL and 55%, respectively, suggest an increased risk for hereditary hemochromatosis and the need for further investigation 1. The most recent and highest quality study, the EASL clinical practice guidelines on haemochromatosis 1, recommends the assessment of serum iron parameters, including transferrin saturation and serum ferritin, as the first step in testing for haemochromatosis.

From the Research

Blood Tests for Hemochromatosis

  • Transferrin saturation (TS) is a key test for diagnosing hemochromatosis, with optimal thresholds being > or =46% 2
  • Unbound iron-binding capacity (UIBC) is also used, with optimal thresholds being < or =28 micromol/L 2
  • Serum ferritin is a useful marker for iron overload, but its correlation with body iron stores is not very strong, even in patients with the C282Y mutation 3
  • Genetic testing for the C282Y mutation of the HFE gene can also be used to diagnose hemochromatosis 2

Blood Tests for Wilson's Disease

  • There are no research papers provided to assist in answering this question

Common Blood Tests for Iron-Related Disorders

  • Serum ferritin is a key test for diagnosing iron deficiency, with levels <30 ng/mL indicating iron deficiency 4
  • Transferrin saturation (TS) can also be used to diagnose iron deficiency, with levels <20% indicating iron deficiency 4
  • Serum iron and total iron binding capacity (TIBC) are not recommended as primary tests for diagnosing iron deficiency, as they provide no additional information when serum ferritin is available 5

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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