What are the other Names for this Condition? (Also known as/Synonyms)

• Hereditary Iron-Handling Disorder
• Hypochromic Microcytic Anemia with Defect in Iron Metabolism
• IRIDA Syndrome

What is Iron-Refractory Iron Deficiency Anemia? (Definition/Background Information)

• Iron-Refractory Iron Deficiency Anemia (IRIDA) is a type of iron deficiency anemia that typically does not improve with oral iron treatment
• Children with IRIDA have too little iron in their blood, which causes their red blood cells to be small (microcytic) and pale (hypochromic). The anemia tends to be mild to moderate, but without enough healthy red blood cells, different parts of the body do not get enough oxygen
• Symptoms of Iron-Refractory Iron Deficiency Anemia are usually mild, but may include pale skin and in some cases, feeling weak, tired, or dizzy. Growth and development of a child with IRIDA is usually normal
• Iron-Refractory Iron Deficiency Anemia is caused by changes or mutations in the TMPRSS6 gene and inheritance is autosomal recessive
• Iron-Refractory Iron Deficiency Anemia is usually suspected in childhood due to the results of routine blood tests, but the diagnosis is confirmed by genetic testing
• Treatment may first involve a trial of oral iron along with vitamin C for several weeks. If there is little to no improvement, treatment usually involves intravenous (IV) iron therapy, which may partially improve the anemia

(Source: Iron-Refractory Iron Deficiency Anemia; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets Iron-Refractory Iron Deficiency Anemia? (Age and Sex Distribution)

• Iron-Refractory Iron Deficiency Anemia is a rare congenital disorder with just about 50 cases reported in the medical literature
• The presentation of symptoms may occur at birth 
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Iron-Refractory Iron Deficiency Anemia? (Predisposing Factors)

• A positive family history may be an important risk factor, since Iron-Refractory Iron Deficiency Anemia can be inherited
• Currently, no other risk factors have been clearly identified for this condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Iron-Refractory Iron Deficiency Anemia? (Etiology)

• Iron-Refractory Iron Deficiency Anemia is caused by mutations in the TMPRSS6 gene 
• This gene codes for a protein matriptase 2, which helps regulate iron levels in the body
• IRIDA is inherited in an autosomal recessive manner

Autosomal recessive pattern of inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Iron-Refractory Iron Deficiency Anemia?

The signs and symptoms of Iron-Refractory Iron Deficiency Anemia may vary among affected individuals in type and severity. Based on the frequency of symptoms observed, the following information may be noted:

• Abnormality of the intestine
• Anisocytosis
• Hyperkeratosis
• Hypocupremia
• Hypochromic microcytic anemia
• Ichthyosis
• Intellectual disability
• Intrahepatic cholestasis
• Pallor
• Peripheral neuropathy
• Poikilocytosis

(Source: Iron-Refractory Iron Deficiency Anemia; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

How is Iron-Refractory Iron Deficiency Anemia Diagnosed?

Iron-Refractory Iron Deficiency Anemia is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Iron-Refractory Iron Deficiency Anemia?

The complications of Iron-Refractory Iron Deficiency Anemia may include:

• Extreme tiredness, listlessness
• Episodes of fainting

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Iron-Refractory Iron Deficiency Anemia Treated?

The treatment methods for Iron-Refractory Iron Deficiency Anemia may include:

• High doses of oral iron, prolonged oral iron therapy, or oral iron therapy combined with vitamin C for those individuals who show partial response to treatment 
• Intravenous iron therapy, if no improvement is observed with other forms of iron supplementation

How can Iron-Refractory Iron Deficiency Anemia be Prevented?

Iron-Refractory Iron Deficiency Anemia may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Iron-Refractory Iron Deficiency Anemia? (Outcomes/Resolutions) 

• The prognosis of Iron-Refractory Iron Deficiency Anemia is good, as the signs and symptoms are mild, and affected children generally exhibit normal growth and development
• Additionally, based on the available data on follow-up of individuals with IRIDA into adulthood, it appears that the long-term effect of the disorder is limited, and that the signs and symptoms of IRIDA continue to resolve with age

Additional and Relevant Useful Information for Iron-Refractory Iron Deficiency Anemia:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/