Should a young healthy male with elevated iron saturation, normal ferritin (Ferritin) levels, and low Total Iron-Binding Capacity (TIBC) be tested for hereditary hemochromatosis?

From the Guidelines

Testing for hemochromatosis is warranted in this case due to the elevated transferrin saturation of 71% and altered iron metabolism indicators, despite normal ferritin levels. The patient's iron % saturation of 71% is concerning, as a saturation above 45% is one of the key screening markers for hereditary hemochromatosis 1. Although the ferritin level is within normal range (375), the high saturation with low TIBC indicates altered iron metabolism that warrants investigation. Some key points to consider in this case include:

• The American College of Physicians recommends risk-stratifying patients with associated conditions such as liver disease, cardiac arrhythmias, or family history of hereditary hemochromatosis 1.
• The initial symptoms associated with iron overload might be nonspecific, and the decision to perform tests should be based on clinical judgment regarding what may cause such protean manifestations 1.
• Genetic testing for the HFE gene mutations (particularly C282Y and H63D) may be considered, as these are responsible for most cases of hereditary hemochromatosis.
• Early detection is important because hemochromatosis can lead to organ damage over time as iron accumulates, and treatment (regular phlebotomy) is simple and effective when started before complications develop.
• Other causes of elevated transferrin saturation should also be considered, including liver disease, alcohol consumption, and certain medications, so a complete clinical evaluation would be beneficial alongside genetic testing.

From the Research

Iron Overload and Hemochromatosis

• The patient's iron % saturation is 71%, which is elevated, indicating potential iron overload 2.
• However, the patient's ferritin level is normal (375), and TIBC is low, which may suggest that the iron overload is not due to hemochromatosis 2.
• The total iron level is 163, which is not significantly elevated, but should be considered in the context of other laboratory results.

Considerations for Hemochromatosis Testing

• Hemochromatosis is a rare genetic disorder characterized by iron overload, and can be diagnosed through laboratory testing for serum ferritin and transferrin saturation 2.
• Genetic testing for the HFE mutation can be performed in patients with elevated iron indices and a suspicion for hemochromatosis or liver disease 2.
• Given the patient's elevated iron % saturation and low TIBC, further testing for hemochromatosis may be warranted, despite normal ferritin levels 2.

Treatment Options for Iron Overload

• Phlebotomy is a common treatment for patients with hereditary hemochromatosis, aimed at removing excess iron stores 2, 3.
• Erythrocytapheresis is an alternative treatment option that can achieve iron depletion more quickly than manual phlebotomies 3.