Iron refractory iron deficiency anemia

Abstract

Iron refractory iron deficiency anemia is a hereditary recessive anemia due to a defect in the TMPRSS6 gene encoding Matriptase-2. This protein is a transmembrane serine protease that plays an essential role in down-regulating hepcidin, the key regulator of iron homeostasis. Hallmarks of this disease are microcytic hypochromic anemia, low transferrin saturation and normal/high serum hepcidin values. The anemia appears in the post-natal period, although in some cases it is only diagnosed in adulthood. The disease is refractory to oral iron treatment but shows a slow response to intravenous iron injections and partial correction of the anemia. To date, 40 different Matriptase-2 mutations have been reported, affecting all the functional domains of the large ectodomain of the protein. In vitro experiments on transfected cells suggest that Matriptase-2 cleaves Hemojuvelin, a major regulator of hepcidin expression and that this function is altered in this genetic form of anemia. In contrast to the low/undetectable hepcidin levels observed in acquired iron deficiency, in patients with Matriptase-2 deficiency, serum hepcidin is inappropriately high for the low iron status and accounts for the absent/delayed response to oral iron treatment. A challenge for the clinicians and pediatricians is the recognition of the disorder among iron deficiency and other microcytic anemias commonly found in pediatric patients. The current treatment of iron refractory iron deficiency anemia is based on parenteral iron administration; in the future, manipulation of the hepcidin pathway with the aim of suppressing it might become an alternative therapeutic approach

Inter-ethnic differences in genetic variants within the transmembrane protease, serine 6 (TMPRSS6) gene associated with iron status indicators: a systematic review with meta-analyses

“…It had generally been thought that TMPRSS6 polymorphisms affect hepcidin transcription, thereby altering hepcidin concentrations in response to systemic iron concentrations (Du et al 2008;Finberg et al 2008;De Falco et al 2013). However, two recent studies Galesloot et al 2013) did not confirm an intermediate role for hepcidin in the SNP-iron status parameters associations.…”

Assessment of subjective sleep quality in iron deficiency anaemia

“…Just like in our country, iron deficiency is the most common cause of anemia in the world and is more prevalent in women than men 2,3 . It has been known that more than 30% of those attending to hospitals in developed countries are anemic and the said ratio is much higher in developing countries.…”

Iron deficiency: new insights into diagnosis and treatment

“…Iron parameters differentiate IRIDA from other microcytic anemias, 29 and a normal C-reactive protein level from anemia of inflammation. Measuring serum hepcidin might be useful in IRIDA, because levels are abnormally high (or normal but inappropriately high) 30 considering the iron deficiency. At present, hepcidin assays are used for research but are not widely available for diagnostic purposes.…”