Iron-refractory iron deficiency anemia (IRIDA) is a rare,
inherited form of iron
deficiency anemia. Iron deficiency anemia occurs when red blood cell counts
are low due to a lack of iron.
Dana-Farber/Boston Children's is an
international leader in the diagnosis and management of rare iron disorders. Through our Rare
Anemias and Iron Disorders Program, children and families with rare iron disorders such as IRIDA have access to world-renown
multidisciplinary teams of hematologists, pathologists and researchers.
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.
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:
Symptoms of iron deficiency include:
In rare cases, children with iron deficiency anemia may also
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 (“sprue”).
In order to distinguish IRIDA from
other, more common forms of iron deficiency anemia, doctors will look for these
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.
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.
IRIDA was first identified in 2008, when researchers at
Dana-Farber/Boston Children’s discovered that most children and adults with a
type of iron deficiency anemia that doesn’t respond to iron supplementation
seemed to harbor mutations in the TMPRSS6
gene. This research led to the recognition of a new clinical entity:
iron-refractory iron deficiency anemia (IRIDA). Since that time,
Dana-Farber/Boston Children’s researchers continue to lead the way in research
and treatment of IRIDA – including building our understanding of the clinical
features of IRIDA and performing genetic studies of IRIDA.
If you, your child, or other family members have the key features of
IRIDA as described in the diagnosis section above, we invite you to contact us
for an evaluation or to learn more about our research. We have an open research
protocol that is helping to build our understanding of the key features and
genetic underpinnings of IRIDA. Through this protocol, children and adults who
choose to participate will agree to provide blood and urine samples. Our
researchers will then use those samples to assess iron proteins in the blood,
hepcidin level in the blood and urine, and to sequence the TMPRSS6 gene. In ongoing work, the team is working toward
identifying other genes responsible for IRIDA and is using a novel test for
hepcidin to discriminate patients with IRIDA from patients with complicated
acquired iron deficiency. This testing is being performed primarily to increase
scientific knowledge. However, if an individual’s test reveals information that
could be of clinical benefit, those results will be returned to you and your
doctor so that they can be confirmed in a certified diagnostic laboratory – as
long as you indicate an interest in the results when signing up for the study.
To learn more about the study, contact Mark
D. Fleming, MD, DPhil at
Our Published Research