Iron-Refractory Iron Deficiency Anemia (IRIDA) is a rare genetic disorder that causes persistent iron deficiency anemia that does not respond to oral iron supplementation. It is caused by mutations in the TMPRSS6 gene, which leads to excessive production of hepcidin, a hormone that blocks iron absorption from the intestines and release from body stores. The Serum Iron Test is the most important test for diagnosis, as it reveals characteristically low circulating iron levels despite normal or elevated iron stores in the body.
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Iron-Refractory Iron Deficiency Anemia is caused by mutations in the TMPRSS6 gene, which is inherited in an autosomal recessive pattern. This genetic defect leads to overproduction of hepcidin, a hormone that regulates iron metabolism by blocking iron absorption in the intestines and preventing iron release from storage sites in the body. The result is a paradoxical situation where the body has normal or even high iron stores but cannot access that iron for red blood cell production, leading to persistent anemia that resists standard oral iron supplementation.
The Serum Iron Test is the most important test for IRIDA because it reveals the characteristic pattern of persistently low circulating iron levels that fail to respond to oral iron therapy. This test measures the amount of iron in your bloodstream and helps distinguish IRIDA from typical iron deficiency anemia. Healthcare providers often combine this with additional tests like ferritin levels, transferrin saturation, and complete blood count to see the full picture. The hallmark finding is low serum iron despite normal or elevated ferritin, indicating that iron is stored but not accessible for use. Genetic testing for TMPRSS6 mutations can confirm the diagnosis when blood tests show this unusual pattern.
You should get tested if you have been diagnosed with iron deficiency anemia that does not improve despite taking oral iron supplements for several months. Other red flags include persistent fatigue, weakness, and pale skin that continue even with treatment, or if you have a family history of unusual anemia that runs in your family. Testing is especially important if your doctor has tried multiple types of oral iron supplements without success, as this resistance to oral therapy is the defining feature of IRIDA and requires a different treatment approach, typically involving intravenous iron administration.
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What this means
Your iron levels are below the optimal range, which may explain feelings of fatigue, weakness, or difficulty concentrating. Low iron reduces your body's ability to transport oxygen efficiently, impacting your energy and physical performance. Addressing this through diet or supplementation can help restore your vitality.
Recommended actions
Increase iron-rich foods like red meat, chicken, fish, beans, lentils, and fortified cereals
Pair iron sources with vitamin C foods (citrus, tomatoes, peppers) to boost absorption
Avoid tea and coffee with meals as they inhibit iron absorption
Consider retesting in 2-3 months after dietary changes or supplementation
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