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J Investig Med High Impact Case Rep. 2017 Apr 19;5(2):2324709617701776. doi: 10.1177/2324709617701776. eCollection 2017 Apr-Jun.

Iron Refractory Iron Deficiency Anemia in Dizygotic Twins Due to a Novel TMPRSS6 Gene Mutation in Addition to Polymorphisms Associated With High Susceptibility to Develop Ferropenic Anemia.

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Universidade de Lisboa, Lisboa, Portugal.
Hospital de Santa Maria, Lisboa, Portugal.
Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Portugal.


Iron refractory iron deficiency anemia (IRIDA) is an autosomal recessive ferropenic anemia. Its hypochromic microcytic pattern is associated with low transferrin saturation, normal-high ferritin, and inappropriately high hepcidin level. This entity is caused by mutants of the TMPRSS6 gene that encodes the protein matriptase II, which influences hepcidin expression, an iron metabolism counterregulatory protein. We report two 29-year-old dizygotic female twins with ferropenic, hypochromic microcytic anemia with 20 years of evolution, refractory to oral iron therapy. After exclusion of gastrointestinal etiologies, IRIDA diagnosis was suspected and a novel mutation in the TMPRSS6 gene was identified. It was found in intron 11 (c.1396+4 A>T) and seems to affect the gene expression. In addition, 3 polymorphisms already associated with a higher risk of developing iron deficiency anemia were also found (D521D, V736A, and Y739Y). Our case reports an undescribed mutation causing IRIDA and supports the hypothesis that this clinical syndrome may be more common than previously thought and its genetics more heterogeneous than initially described.


anemia; deficiency; iron; mutation; refractory

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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