IRIDA syndrome

IRIDA syndrome (Iron-Refractory Iron Deficiency Anemia) is a rare inherited form of iron deficiency anemia caused by mutations in the TMPRSS6 gene, which encodes a transmembrane serine protease called matriptase-2. This protein plays a critical role in regulating hepcidin, the master hormone controlling iron absorption from the gut. In IRIDA, loss of matriptase-2 function leads to inappropriately elevated hepcidin levels, which block intestinal iron absorption and impair iron release from body stores. As a result, patients develop iron deficiency anemia that does not respond to oral iron supplementation — a hallmark feature that distinguishes IRIDA from common nutritional iron deficiency. The condition typically presents in infancy or childhood with microcytic hypochromic anemia, very low serum iron and transferrin saturation, and low-to-normal ferritin levels. Patients may experience fatigue, pallor, weakness, and poor exercise tolerance. A key diagnostic clue is the failure to respond to standard oral iron therapy, combined with an incomplete or slow response even to intravenous iron supplementation. Hepcidin levels are inappropriately high relative to the degree of iron deficiency, which is unusual since hepcidin is normally suppressed when iron stores are low. Treatment of IRIDA is challenging. Oral iron is ineffective due to the hepcidin-mediated block in intestinal iron absorption. Parenteral (intravenous) iron therapy can partially improve hemoglobin levels, though the response is often incomplete and transient, requiring repeated infusions. There is no curative therapy currently available, and management focuses on maintaining adequate hemoglobin levels through periodic intravenous iron administration. Research into hepcidin-lowering therapies may offer future treatment options. Genetic testing of the TMPRSS6 gene confirms the diagnosis and enables genetic counseling for affected families.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about IRIDA syndrome