Iron-refractory iron deficiency anemia.
Iron-refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder characterized by iron deficiency anemia unresponsive to oral iron treatment but partially responsive to parenteral iron therapy. IRIDA has recently been shown to be caused by mutations in the gene TMPRSS6, which encodes a transmembrane serine protease (also known as matriptase-2) expressed by the liver. IRIDA patients show inappropriately elevated levels of hepcidin, a circulating hormone produced by the liver that inhibits both iron absorption from the intestine and iron release from macrophage stores. Recent studies suggest that TMPRSS6 normally acts to downregulate hepcidin expression by cleaving hemojuvelin, a membrane-bound protein that promotes hepcidin signaling in hepatocytes. A discussion of the clinical presentation of IRIDA, the molecular genetics of this disorder, and recent studies elucidating the underlying pathophysiology are presented.
Finberg
Karin E
KE
Department of Pathology, Duke University Medical Center, Durham, NC.
D000284:Administration, Oral; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D000753:Anemia, Refractory / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D058851:GPI-Linked Proteins; D006397:Hematinics / Q000008:administration & dosage*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D006801:Humans; D007223:Infant; D007263:Infusions, Parenteral; D007501:Iron / Q000097:blood / Q000378:metabolism*; D058085:Iron Compounds / Q000008:administration & dosage*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D012697:Serine Endopeptidases / Q000235:genetics; D017211:Treatment Failure; D015854:Up-Regulation
D023181:Antimicrobial Cationic Peptides; D058851:GPI-Linked Proteins; C578702:HAMP protein, human; C481006:HJV protein, human; D006397:Hematinics; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D058085:Iron Compounds; D008565:Membrane Proteins; D007501:Iron; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human