From the Guidelines
For heterozygous hereditary hemochromatosis (HH), the recommended laboratory tests include serum ferritin, transferrin saturation, and complete blood count, with the first step in testing being the assessment of serum iron parameters, which should include transferrin saturation and serum ferritin 1. These tests should be performed to monitor iron levels, as heterozygous carriers typically have milder iron overload than homozygotes but may still develop elevated iron stores over time.
- Serum ferritin measures stored iron, while transferrin saturation indicates the percentage of iron-binding sites that are occupied.
- A comprehensive metabolic panel is also useful to assess liver function, as mild hepatic involvement can occur.
- Genetic testing for HFE gene mutations (particularly C282Y and H63D) can confirm carrier status if not already established.
- If ferritin or transferrin saturation levels are elevated, additional testing may include liver function tests and possibly liver imaging or biopsy in select cases. These laboratory tests are important because even heterozygous carriers can sometimes develop clinically significant iron overload, particularly when combined with other risk factors like alcohol consumption, viral hepatitis, or metabolic syndrome. Regular monitoring allows for early intervention with phlebotomy if iron levels become significantly elevated, as recommended by the European Association for the Study of the Liver (EASL) clinical practice guidelines on haemochromatosis 1.
From the Research
Diagnosis of Heterozygous Hereditary Hemochromatosis (HH)
To diagnose heterozygous hereditary hemochromatosis (HH), several laboratory tests are recommended:
- Transferrin saturation (calculated as serum iron/total iron binding capacity × 100) 2
- Serum ferritin concentrations 3, 2
- Serum iron concentration 3
- Total iron binding capacity (TIBC) 3
- Liver iron quantification by SQUID-biosusceptometry 4
Laboratory Tests
The following laboratory tests can be used to assess iron stores and diagnose HH:
- Serum ferritin level: Although it has some limitations, serum ferritin level is considered the best predictor of body iron stores 5
- Transferrin saturation: A transferrin saturation >45% with or without hyperferritinemia is an indication for further testing for the hemochromatosis gene 2
- Liver biopsy: Can be used to distinguish iron overload due to HLA-linked hereditary hemochromatosis from other causes of hemochromatosis 3
Limitations of Laboratory Tests
It is essential to note that:
- Serum ferritin level can be influenced by non-iron related factors such as inflammation 4
- Ferritin iron content is not a reliable parameter for assessing individual liver iron concentrations 4
- Transferrin saturation may not always be elevated in patients with iron overload, especially in those with low or normal transferrin saturation 2