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Iron-refractory iron deficiency anemia
Reviewed by Medicinsk Expert•Last updated: 2026-10-22•Condition

Iron-refractory iron deficiency anemia

Iron-refractory iron deficiency anemia (IRIDA) is a genetic form of anemia where the body cannot properly regulate iron, making the condition resistant to standard iron supplementation.

Overview

Iron-refractory iron deficiency anemia (IRIDA) is a type of anemia characterized by a shortage of healthy red blood cells. It is defined as "iron-refractory" because it is totally resistant to oral iron treatment and only partially responsive to intravenous iron. In affected individuals, red blood cells are abnormally small (microcytic) and pale (hypochromic).

Symptoms

Symptoms are typically most pronounced during childhood, though they are generally mild. They include:

  • Tiredness (fatigue)
  • Weakness
  • Pale skin

Despite these symptoms, affected individuals usually experience normal growth and development.

Causes

The condition is caused by mutations in the TMPRSS6 gene. This gene provides instructions for making a protein called matriptase-2, which regulates iron levels in the body. When matriptase-2 is absent or nonfunctional, the body cannot regulate iron properly, leading to a shortage in the bloodstream. Because iron is an essential component of hemoglobin—the molecule in red blood cells that carries oxygen—a deficiency results in the production of small, pale red blood cells that cannot effectively transport oxygen.

Inheritance

This condition is inherited in an autosomal recessive pattern. Both copies of the TMPRSS6 gene in each cell must have mutations for the condition to manifest. Parents of an affected individual are typically carriers who do not show signs or symptoms of the disorder.

Frequently Asked Questions

In IRIDA, genetic mutations in the TMPRSS6 gene disable the production of matriptase-2, an enzyme responsible for keeping the hormone hepcidin in check. Without matriptase-2, the liver produces excessively high levels of hepcidin, which degrades ferroportin channels in the gut. Because ferroportin is destroyed, iron ingested through diet or pills cannot cross the intestinal wall into the bloodstream and is instead eliminated unused.
patient with IRIDA typically presents with markedly low serum iron levels and very low transferrin saturation (often below 10%), accompanied by severe microcytosis and hypochromia. Unlike common dietary iron deficiency, where hepcidin levels drop to near zero to promote absorption, patients with IRIDA demonstrate inappropriately normal or elevated serum hepcidin levels alongside a complete lack of reticulocyte response after a monitored oral iron challenge.
Genetic testing is indicated in infants or young children who present with chronic, microcytic hypochromic anemia that shows zero hematologic improvement after at least four to eight weeks of confirmed, compliant oral iron therapy. Testing is pursued after common secondary causes of malabsorption, such as celiac disease, autoimmune gastritis, chronic gastrointestinal bleeding, and Helicobacter pylori infection, have been ruled out.
Treatment relies on intravenous (IV) iron therapy, although the response is slower and only partial compared to patients with non-genetic iron deficiencies. Repeated or higher doses of modern IV iron formulations are typically administered to bypass the blocked intestinal tract. The goal of therapy is usually to keep hemoglobin at a functional, safe baseline and support normal child development rather than attempting to fully normalize ferritin levels.
Source: MedlinePlus, National Library of Medicine

MedlinePlus brings together authoritative health information from the National Library of Medicine (NLM), the National Institutes of Health (NIH), and other government agencies and health-related organizations.

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