IRIDA | Symptoms & Causes
What are the symptoms of iron-refractory iron deficiency anemia?
The symptoms of iron-refractory iron deficiency anemia (IRIDA) in children are similar to the symptoms of all forms of anemia and iron deficiency.
Typical anemia symptoms include:
- fatigue, weakness
- irritability
- exercise/feeding intolerance
- exertional dyspnea
- headache, vertigo
- pale skin
Symptoms of iron deficiency include:
- pica (craving of non-food items – such as clay, dirt, paper, ice, baby powder, starch)
- poor sleep or restless leg syndrome
- angular cheilitis (sore lesions at the corners of the mouth)
In rare cases, children with iron deficiency anemia may also experience:
- nail changes (koilonychia or spoon nails)
- alopecia (hair loss) is rarely experienced
- atrophic glossitis (tongue swelling/pain or dry mouth)
- dysphagia (difficulty swallowing)
What causes IRIDA?
IRIDA is caused by mutations in the gene TMPRSS6. It is inherited as an autosomal recessive disorder, which means both parents must have a copy of the gene mutation and pass it on to their child. Therefore it may be seen in several of the child’s family members. The TMPRSS6 gene encodes a particular liver protein that regulates the production of hepcidin, an iron regulatory hormone. In children with IRIDA, the TMPRSS6 mutation causes elevated levels of hepcidin, which ultimately impairs the body’s ability to both absorb and use iron. There is some evidence that relatives that carry one abnormal copy of TMPRSS6 (e.g., parents) are more susceptible to acquired iron deficiency.
IRIDA | Diagnosis & Treatments
How is iron-refractory iron deficiency anemia diagnosed?
The first step in treating your child is providing an accurate and complete diagnosis. General iron deficiency anemia can be identified through a complete blood count, an analysis that involves measuring the size, number and maturity of different blood cells within a set volume of blood.
If your child is determined to have iron deficiency anemia, doctors will want to rule out possible causes of acquired iron deficiency, such as gastrointestinal blood loss; causes of small red blood cells (microcytosis), such as thalassemias or lead toxicity; or chronic inflammatory disorders or intestinal malabsorption, such as celiac disease.
In order to distinguish IRIDA from other, more common forms of iron deficiency anemia, doctors will look for these key features:
- lifelong anemia (hemoglobin 6-9 g/dL)
- very low red blood cell size (microcytic), with a mean corpuscular volume (MCV) of 45-65 fL
- very low iron levels in the blood (transferrin saturation <5%)
- abnormal oral iron absorption – no response to oral iron supplements or failure of an “oral iron challenge” (see below)
- abnormal iron utilization – a slow, incomplete, and transient response to parenteral iron (iron injected intravenously)
- other affected family members with an autosomal recessive inheritance pattern
If your child has most or all of these features, doctors can confirm the diagnosis by measuring the blood level of the hepcidin hormone in your child.
You may also choose to have your child participate in a research protocol at Dana-Farber/Boston Children’s, in which your child’s TMPRSS6 gene is sequenced. The gene sequencing can confirm an IRIDA diagnosis, and over time this research may help reveal opportunities to improve treatment. In addition, if mutations in TMPRSS6 are not found, the research team is actively looking for other causes of inherited iron deficiency.
What is the oral iron challenge?
The oral iron challenge is an easy test provided in a doctor’s office. First, your child will have a blood test to check anemia and iron levels. This will be followed by a dose of oral iron. About 90 minutes later, your child will receive a second blood test to check iron levels again. The iron level in the blood should rise significantly. If the iron level does not rise, it suggests either a problem with the small bowel or IRIDA.
How is IRIDA treated?
Because the iron deficiency of IRIDA is refractory (does not respond) to oral iron supplementation and usually is only partially responsive to parenteral iron, your child may receive repeated infusions of intravenous iron. These repeated iron infusions can improve the anemia, microcytosis and iron stores (ferritin). However, the serum iron and transferrin saturation generally do not improve to the normal range, and if your child stops receiving regular intravenous iron infusions, the previous low iron levels and microcytic anemia almost certainly will appear again.
