Iron-refractory iron deficiency anemia (IRIDA) cases with 2 novel TMPRSS6 mutations

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder.
• It is caused by mutations in the TMPRSS6 gene, encoding matriptase-2.
• Unlike typical iron deficiency anemia, IRIDA features elevated serum hepcidin levels.

Purpose of the Study:

• To report cases of IRIDA diagnosed due to inadequate response to iron therapy.
• To highlight the genetic basis and clinical presentation of IRIDA.
• To emphasize the importance of considering IRIDA in specific patient populations.

Main Methods:

• Clinical case reporting of 5 patients from 4 families.
• Genetic analysis to identify mutations in the TMPRSS6 gene.
• Assessment of response to iron therapy and serum hepcidin levels.

Main Results:

• Five cases diagnosed with IRIDA, with a mean age of 5.0 years.
• All patients had homozygous or compound heterozygous mutations in TMPRSS6, including two novel mutations (Cys410Ser, Leu689Pro).
• Patients showed inadequate response to oral iron therapy, with normal or elevated serum ferritin.

Conclusions:

• IRIDA should be suspected in patients with iron deficiency anemia unresponsive to oral iron.
• Genetic testing of the TMPRSS6 gene is crucial for diagnosing IRIDA.
• Understanding IRIDA's distinct pathophysiology is vital for appropriate patient management.