Rare anemias due to genetic iron metabolism defects

Mutat Res Rev Mutat Res. 2018 Jul-Sep;777:52-63. doi: 10.1016/j.mrrev.2018.06.003. Epub 2018 Jun 22.


Anemia is defined by a deficiency of hemoglobin, an iron-rich protein that binds oxygen in the blood. It can be due to multiple causes, either acquired or genetic. Alterations of genes involved in iron metabolism may be responsible, usually at a young age, for rare forms of chronic and often severe congenital anemia. These diseases encompass a variety of sideroblastic anemias, characterized by the presence of ring sideroblasts in the bone marrow. Clinical expression of congenital sideroblastic anemia is either monosyndromic (restricted to hematological lineages) or polysyndromic (with systemic expression), depending on whether iron metabolism, and especially heme synthesis, is directly or indirectly affected. Beside sideroblastic anemias, a number of other anemias can develop due to mutations of key proteins acting either on cellular iron transport (such as the DMT1 transporter), plasma iron transport (transferrin), and iron recycling (ceruloplasmin). Contrasting with the aforementioned entities which involve compartmental, and sometimes, systemic iron excess, the iron refractory iron deficiency anemia (IRIDA) corresponds to a usually severe anemia with whole body iron deficiency related to chronic increase of plasma hepcidin, the systemic negative regulator of plasma iron. Once clinically suggested, these diseases are confirmed by genetic testing in specialized laboratories.

Keywords: Aceruloplasminemia; Anemia; Atransferrinemia; Congenital sideroblastic anemia; DMT1; Ferroportin; Gene mutation; IRIDA; Iron; Matriptase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anemia / etiology
  • Anemia / genetics*
  • Animals
  • Heme / biosynthesis
  • Humans
  • Intestinal Absorption
  • Iron / metabolism*
  • Iron Overload / genetics
  • Mitochondria / physiology
  • Mutation*
  • Rare Diseases / etiology
  • Rare Diseases / genetics*


  • Heme
  • Iron