What are the diagnostic blood tests for hereditary hemochromatosis (HH)?

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From the Guidelines

The diagnostic blood tests for hereditary hemochromatosis (HH) include transferrin saturation and serum ferritin tests as initial screening, followed by genetic testing for HFE gene mutations if these are elevated. The initial screening tests are crucial in identifying individuals with iron overload, which is a hallmark of hereditary hemochromatosis 1.

Key Diagnostic Tests

  • Transferrin saturation: This test measures the percentage of transferrin that is saturated with iron. A level above 45% is considered elevated and may indicate iron overload 1.
  • Serum ferritin: This test measures the level of ferritin in the blood, which is a protein that stores iron. Elevated levels of ferritin can indicate iron overload 1.

Additional Tests

Additional tests may include:

  • Complete blood count (CBC) to assess for anemia or other blood disorders
  • Liver function tests (LFTs) to assess for liver damage
  • Blood glucose to assess for diabetes
  • Genetic testing for HFE gene mutations, particularly C282Y and H63D, to confirm hereditary hemochromatosis 1

Importance of Early Detection

Early detection and treatment of hereditary hemochromatosis are crucial in preventing serious complications such as liver cirrhosis, diabetes, and heart problems 1. Regular monitoring of ferritin levels every 3-6 months during treatment and annually thereafter is recommended to ensure that iron levels remain within a safe range 1.

Treatment

Treatment typically involves therapeutic phlebotomy (removal of 500mL of blood) weekly until ferritin levels normalize (below 50-100 ng/mL), followed by maintenance phlebotomies 2-4 times yearly 1.

From the Research

Diagnostic Blood Tests for Hereditary Hemochromatosis (HH)

The diagnostic blood tests for hereditary hemochromatosis (HH) include:

  • Serum ferritin level: Elevated ferritin levels can indicate iron overload, which is a hallmark of HH 2, 3, 4, 5, 6
  • Transferrin saturation (TSAT): TSAT is calculated as serum iron/total iron binding capacity × 100, and elevated TSAT levels can suggest HH 3, 4, 5, 6
  • Genetic testing for HFE gene mutations: Specifically, testing for the C282Y and H63D mutations, which are commonly associated with HH 2, 3, 4, 5

Interpretation of Blood Test Results

The interpretation of blood test results for HH diagnosis is as follows:

  • Elevated ferritin levels and TSAT >45% in females and TSAT >50% in males and postmenopausal women can suggest provisional iron overload and diagnose HH in patients homozygous for p.Cys282Tyr in HFE 5
  • In patients with high TSAT and elevated ferritin but other HFE genotypes, diagnosis requires the presence of hepatic iron overload on MRI or liver biopsy 5
  • Low or normal TSAT with high serum ferritin levels should alert the physician to other causes of iron overload besides HH 6

Additional Diagnostic Tests

Additional diagnostic tests that may be used to confirm HH diagnosis or assess disease severity include:

  • Liver biopsy to assess hepatic iron stores and establish the presence or absence of cirrhosis 2, 3, 5
  • Magnetic resonance imaging (MRI) with quantitative assessment of iron content to evaluate hepatic iron overload 2, 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Iron overload disorders.

Hepatology communications, 2022

Research

Diagnosis of hemochromatosis.

Annals of internal medicine, 1998

Research

Epidemiology and diagnostic testing for hemochromatosis and iron overload.

International journal of laboratory hematology, 2015

Research

[Recommendations of EASL clinical practice guidelines on haemochromatosis].

Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology, 2022

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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