[Iron deficiency anaemia due to a matriptase-2 mutation].
A 36-year old female patient who had had iron deficiency anaemia since her childhood showed no clear response to oral iron treatment. Elevated serum hepcidin levels were found after excluding other causes of iron deficiency. This is in contrast to what is expected in iron deficiency anaemia and indicates a primary defect in hepcidin regulation. Indeed, in the search for a defect in genes coding for hepcidin-regulating proteins the patient was found to be compound heterozygous for two different mutations in the TMPRSS6 gene. This leads to a dysfunctional matriptase-2 protein for which the gene codes. Consequently, liver cells cannot inhibit hepcidin production in the presence of low serum iron levels. High hepcidin levels result in less iron being absorbed from the bowel than is necessary for erythropoiesis. Therefore, patients with matriptase-2 deficiency respond poorly to oral iron treatment and have to be treated with intravenous iron.
Cuijpers
M L H Marloes
ML
Universitair Medisch Centrum St. Radboud, Nijmegen, Afd. Hematologie, the Netherlands.
Wiegerinck
Erwin T G
ET
Brouwer
Rick
R
de Witte
Theo J M
TJ
Swinkels
Dorine W
DW
D000328:Adult; D018798:Anemia, Iron-Deficiency / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics*; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D005260:Female; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000627:therapeutic use; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D017211:Treatment Failure
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D008565:Membrane Proteins; D007501:Iron; D012697:Serine Endopeptidases; C504318:TMPRSS6 protein, human; C467801:matriptase 2