Abstract
Rare hereditary anemias (RHA) represent a group of disorders characterized by either impaired production of erythrocytes or decreased survival (i.e., hemolysis). In RHA, the regulation of iron metabolism and erythropoiesis is often disturbed, leading to iron overload or worsening of chronic anemia due to unavailability of iron for erythropoiesis. Whereas iron overload generally is a well-recognized complication in patients requiring regular blood transfusions, it is also a significant problem in a large proportion of patients with RHA that are not transfusion dependent. This indicates that RHA share disease-specific defects in erythroid development that are linked to intrinsic defects in iron metabolism. In this review, we discuss the key regulators involved in the interplay between iron and erythropoiesis and their importance in the spectrum of RHA.
Highlights
Rare hereditary anemias (RHA) are a heterogenous group of diseases caused by genetic defects, resulting in impaired production or increased destruction of red blood cells (RBCs)
The incidence of hereditary anemias varies, with hereditary spherocytosis, thalassemia and sickle cell disease being the more common, while Diamond-Blackfan anemia, congenital dyserythropoietic anemia and pyruvate kinase deficiency are among the rarer anemias [1,2,3,4]
Most knowledge of iron overload (IO) is based on hereditary hemochromatosis (HH) patients, where iron loading occurs due to mutations in genes involved in iron metabolism
Summary
Rare hereditary anemias (RHA) are a heterogenous group of diseases caused by genetic defects, resulting in impaired production or increased destruction of red blood cells (RBCs). Following blood loss or during chronic anemia, hypoxic conditions induce increased EPO levels, which stimulate ERFE expression by erythroblasts and downregulate hepcidin production to provide extra iron supply to support erythropoiesis. During ineffective erythropoiesis (a state of increased erythroid drive in the bone marrow with premature death of erythroblasts, resulting in a decreased erythroid output), ERFE levels are greatly increased, which is thought to be caused by the increased number of erythroblasts [29] Another protein which may be increased in RHA is Growth and Differentiation Factor 15 (GDF15).
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