Iron Refractory Iron Deficiency Anemia Due to 374 Base Pairs Deletion in the TMPRSS6 Gene

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• Iron refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder characterized by microcytic anemia resistant to oral iron therapy.
• Mutations in the TMPRSS6 gene, encoding matriptase-2, are the primary cause of IRIDA.
• Patients often show limited response to iron supplementation, necessitating alternative management strategies.

Observation:

• A 6-month-old Syrian boy presented with hypochromic-microcytic anemia and normal ferritin levels.
• The patient exhibited resistance to standard oral iron therapy, with hemoglobin levels only improving after red blood cell transfusion.
• Clinical presentation suggested a diagnosis of iron refractory iron deficiency anemia.

Findings:

• Genetic analysis revealed a novel homozygous 374 base pair deletion in exon 15 of the TMPRSS6 gene.
• This specific deletion disrupts the TMPRSS6 gene, consistent with the underlying cause of IRIDA.
• The identified mutation expands the known spectrum of TMPRSS6 gene alterations associated with this condition.

Implications:

• This finding contributes to a deeper understanding of the genetic basis of iron refractory iron deficiency anemia.
• It highlights the importance of comprehensive genetic testing for diagnosing IRIDA, especially in cases unresponsive to iron therapy.
• Expanding the mutation spectrum aids in accurate genetic counseling and potential development of targeted therapies for IRIDA.