From the Guidelines
Hereditary Hemochromatosis (HH) is diagnosed based on elevated transferrin saturation (TSAT) and ferritin levels, with provisional iron overload diagnosed in patients homozygous for p.Cys282Tyr in HFE with TSAT >45% and ferritin >200 µg/L in females and TSAT >50% and ferritin >300 µg/L in males and post-menopausal women, as per the most recent guidelines 1. The diagnostic criteria for HH involve a combination of blood tests, genetic testing, and sometimes liver biopsy or MRI.
- Initial screening involves measuring serum ferritin and transferrin saturation levels, with elevated levels suggesting hemochromatosis.
- Genetic testing for the HFE gene mutations, particularly C282Y, confirms hereditary hemochromatosis, with C282Y homozygosity being the most common cause.
- The European Association for the Study of the Liver guidelines suggest that 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 1. The diagnosis process should prioritize the assessment of liver fibrosis and other end-organ damage, as these determine disease management, and patients with advanced fibrosis should be included in a screening programme for hepatocellular carcinoma 1. It is essential to note that early diagnosis is crucial, as treatment through regular phlebotomy can prevent serious complications such as liver cirrhosis, diabetes, heart problems, and joint damage.
- Screening is recommended for first-degree relatives of affected individuals due to the genetic nature of the condition.
- The diagnosis process should be coordinated by a gastroenterologist or hematologist experienced in managing iron overload disorders. In contrast to older guidelines, the most recent guidelines provide clear diagnostic criteria based on serum iron parameters and genetic testing, making diagnosis more straightforward 1 compared to older studies 1.
From the Research
Diagnostic Criteria for Hereditary Hemochromatosis (HH)
The diagnostic criteria for Hereditary Hemochromatosis (HH) include:
- Measurement of serum transferrin saturation and serum ferritin level 2, 3, 4, 5, 6
- Mutation analysis of the HFE gene, particularly for the C282Y mutation 3, 5
- Liver biopsy to assess hepatic iron stores and establish the presence or absence of cirrhosis 2, 4, 5, 6
- Other tests to identify complications of iron overload, such as specific organ damage 3
Role of Genetic Testing
Genetic testing for the HFE gene is commercially available, but its place in the diagnosis of hemochromatosis is still being evaluated 2. The most useful role for this test is in the detection of hemochromatosis in family members of patients with a proven case of the disease 2.
Screening Strategies
A reasonable screening strategy would start with a serum transferrin saturation, followed by a repeat transferrin saturation in a fasting state and a serum ferritin level if the initial result is abnormal 4. Phenotypic tests, such as serum transferrin-iron saturation, can be used for initial screening to avoid the problem of identifying non-expressing homozygotes 5.