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Iron-refractory iron deficiency anemia(IRIDA)

MedGen UID:
39081
Concept ID:
C0085576
Disease or Syndrome
Synonyms: ANEMIA, HYPOCHROMIC MICROCYTIC, WITH DEFECT IN IRON METABOLISM; IRIDA; IRIDA syndrome; IRON-HANDLING DISORDER, HEREDITARY; PSEUDO-IRON-DEFICIENCY ANEMIA
SNOMED CT: Iron-refractory iron deficiency anemia (722005000); IRIDA syndrome (722005000); IRIDA (iron-refractory iron deficiency anemia) syndrome (722005000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): TMPRSS6 (22q12.3)
 
Monarch Initiative: MONDO:0008788
OMIM®: 206200
Orphanet: ORPHA209981

Definition

Finberg et al. (2008) referred to this phenotype as iron-refractory iron deficiency anemia (IRIDA) and reviewed the key features: a congenital hypochromic, microcytic anemia; a very low mean corpuscular erythrocyte volume; a low transferrin saturation; abnormal iron absorption characterized by no hematologic improvement following treatment with oral iron; and abnormal iron utilization characterized by a sluggish, incomplete response to parenteral iron. The authors noted that although urinary levels of hepcidin (606464) are typically undetectable in individuals with iron deficiency, in 5 individuals with IRIDA urinary hepcidin/creatinine ratios were within or above the normal range. [from OMIM]

Additional description

From MedlinePlus Genetics
Iron-refractory iron deficiency anemia is one of many types of anemia, which is a group of conditions characterized by a shortage of healthy red blood cells. This shortage prevents the blood from carrying an adequate supply of oxygen to the body's tissues.

Iron-refractory iron deficiency anemia results from an inadequate amount (deficiency) of iron in the bloodstream. It is described as "iron-refractory" because the condition is totally resistant (refractory) to treatment with iron given orally and partially resistant to iron given in other ways, such as intravenously (by IV). In people with this form of anemia, red blood cells are abnormally small (microcytic) and pale (hypochromic). The symptoms of iron-refractory iron deficiency anemia can include tiredness (fatigue), weakness, pale skin, and other complications. These symptoms are most pronounced during childhood, although they tend to be mild. Affected individuals usually have normal growth and development.  https://medlineplus.gov/genetics/condition/iron-refractory-iron-deficiency-anemia

Clinical features

From HPO
Anisocytosis
MedGen UID:
66371
Concept ID:
C0221278
Finding
Abnormally increased variability in the size of erythrocytes.
Poikilocytosis
MedGen UID:
67451
Concept ID:
C0221281
Finding
The presence of abnormally shaped erythrocytes.
Hypochromic microcytic anemia
MedGen UID:
124413
Concept ID:
C0271901
Disease or Syndrome
A type of anemia characterized by an abnormally low concentration of hemoglobin in the erythrocytes and lower than normal size of the erythrocytes.
Elevated circulating hepcidin concentration
MedGen UID:
1637596
Concept ID:
C4703592
Finding
Concentration of hepcidin in the blood circulation above the upper limit of normal.

Term Hierarchy

Follow this link to review classifications for Iron-refractory iron deficiency anemia in Orphanet.

Professional guidelines

PubMed

McKay S, Cohran V, Bass LM
Curr Gastroenterol Rep 2023 Jul;25(7):169-173. Epub 2023 Jun 12 doi: 10.1007/s11894-023-00873-w. PMID: 37303027
Van Assche G
Am J Gastroenterol 2013 Dec;108(12):1889-90. doi: 10.1038/ajg.2013.400. PMID: 24300864
Hershko C, Skikne B
Semin Hematol 2009 Oct;46(4):339-50. doi: 10.1053/j.seminhematol.2009.06.002. PMID: 19786202

Recent clinical studies

Etiology

Piatto VB, Ferdinando DLT, Funes HLX
Arq Bras Cir Dig 2022;35:e1645. Epub 2022 Jun 17 doi: 10.1590/0102-672020210002e1645. PMID: 35730874Free PMC Article
Bruno M, De Falco L, Iolascon A
Semin Hematol 2015 Oct;52(4):270-8. Epub 2015 Jun 3 doi: 10.1053/j.seminhematol.2015.05.002. PMID: 26404439
Archer NM, Brugnara C
Crit Rev Clin Lab Sci 2015;52(5):256-72. Epub 2015 Aug 14 doi: 10.3109/10408363.2015.1038744. PMID: 26292073
Beutler E, Van Geet C, te Loo DM, Gelbart T, Crain K, Truksa J, Lee PL
Blood Cells Mol Dis 2010 Jan 15;44(1):16-21. Epub 2009 Oct 8 doi: 10.1016/j.bcmd.2009.09.001. PMID: 19818657Free PMC Article
Hershko C, Skikne B
Semin Hematol 2009 Oct;46(4):339-50. doi: 10.1053/j.seminhematol.2009.06.002. PMID: 19786202

Diagnosis

Gattermann N, Muckenthaler MU, Kulozik AE, Metzgeroth G, Hastka J
Dtsch Arztebl Int 2021 Dec 10;118(49):847-856. doi: 10.3238/arztebl.m2021.0290. PMID: 34755596Free PMC Article
Cappellini MD, Russo R, Andolfo I, Iolascon A
Hematology Am Soc Hematol Educ Program 2020 Dec 4;2020(1):465-470. doi: 10.1182/hematology.2020000158. PMID: 33275715Free PMC Article
Ganz T
Rinsho Ketsueki 2016;57(10):1913-1917. doi: 10.11406/rinketsu.57.1913. PMID: 27725588
Kujovich JL
Obstet Gynecol Clin North Am 2016 Jun;43(2):247-64. Epub 2016 Mar 18 doi: 10.1016/j.ogc.2016.01.009. PMID: 27212091
Heeney MM, Finberg KE
Hematol Oncol Clin North Am 2014 Aug;28(4):637-52, v. Epub 2014 May 28 doi: 10.1016/j.hoc.2014.04.009. PMID: 25064705

Therapy

Kujovich JL
Obstet Gynecol Clin North Am 2016 Jun;43(2):247-64. Epub 2016 Mar 18 doi: 10.1016/j.ogc.2016.01.009. PMID: 27212091
Sal E, Keskin EY, Yenicesu I, Bruno M, De Falco L
Pediatr Hematol Oncol 2016 Apr;33(3):226-32. Epub 2016 Apr 27 doi: 10.3109/08880018.2016.1157229. PMID: 27120435
Finberg KE
Semin Hematol 2009 Oct;46(4):378-86. doi: 10.1053/j.seminhematol.2009.06.006. PMID: 19786206
Hershko C, Skikne B
Semin Hematol 2009 Oct;46(4):339-50. doi: 10.1053/j.seminhematol.2009.06.002. PMID: 19786202
Cui Y, Wu Q, Zhou Y
Kidney Int 2009 Dec;76(11):1137-41. Epub 2009 Sep 23 doi: 10.1038/ki.2009.357. PMID: 19776721Free PMC Article

Prognosis

Donker AE, Schaap CC, Novotny VM, Smeets R, Peters TM, van den Heuvel BL, Raphael MF, Rijneveld AW, Appel IM, Vlot AJ, Versluijs AB, van Gelder M, Granzen B, Janssen MC, Rennings AJ, van de Veerdonk FL, Brons PP, Bakkeren DL, Nijziel MR, Vlasveld LT, Swinkels DW
Am J Hematol 2016 Dec;91(12):E482-E490. doi: 10.1002/ajh.24561. PMID: 27643674Free PMC Article
Kujovich JL
Obstet Gynecol Clin North Am 2016 Jun;43(2):247-64. Epub 2016 Mar 18 doi: 10.1016/j.ogc.2016.01.009. PMID: 27212091
De Falco L, Totaro F, Nai A, Pagani A, Girelli D, Silvestri L, Piscopo C, Campostrini N, Dufour C, Al Manjomi F, Minkov M, Van Vuurden DG, Feliu A, Kattamis A, Camaschella C, Iolascon A
Hum Mutat 2010 May;31(5):E1390-405. doi: 10.1002/humu.21243. PMID: 20232450
Beutler E, Van Geet C, te Loo DM, Gelbart T, Crain K, Truksa J, Lee PL
Blood Cells Mol Dis 2010 Jan 15;44(1):16-21. Epub 2009 Oct 8 doi: 10.1016/j.bcmd.2009.09.001. PMID: 19818657Free PMC Article
Ramsay AJ, Quesada V, Sanchez M, Garabaya C, Sardà MP, Baiget M, Remacha A, Velasco G, López-Otín C
Hum Mol Genet 2009 Oct 1;18(19):3673-83. Epub 2009 Jul 10 doi: 10.1093/hmg/ddp315. PMID: 19592582

Clinical prediction guides

Donker AE, Schaap CC, Novotny VM, Smeets R, Peters TM, van den Heuvel BL, Raphael MF, Rijneveld AW, Appel IM, Vlot AJ, Versluijs AB, van Gelder M, Granzen B, Janssen MC, Rennings AJ, van de Veerdonk FL, Brons PP, Bakkeren DL, Nijziel MR, Vlasveld LT, Swinkels DW
Am J Hematol 2016 Dec;91(12):E482-E490. doi: 10.1002/ajh.24561. PMID: 27643674Free PMC Article
Kujovich JL
Obstet Gynecol Clin North Am 2016 Jun;43(2):247-64. Epub 2016 Mar 18 doi: 10.1016/j.ogc.2016.01.009. PMID: 27212091
De Falco L, Sanchez M, Silvestri L, Kannengiesser C, Muckenthaler MU, Iolascon A, Gouya L, Camaschella C, Beaumont C
Haematologica 2013 Jun;98(6):845-53. doi: 10.3324/haematol.2012.075515. PMID: 23729726Free PMC Article
De Falco L, Totaro F, Nai A, Pagani A, Girelli D, Silvestri L, Piscopo C, Campostrini N, Dufour C, Al Manjomi F, Minkov M, Van Vuurden DG, Feliu A, Kattamis A, Camaschella C, Iolascon A
Hum Mutat 2010 May;31(5):E1390-405. doi: 10.1002/humu.21243. PMID: 20232450
Hershko C, Skikne B
Semin Hematol 2009 Oct;46(4):339-50. doi: 10.1053/j.seminhematol.2009.06.002. PMID: 19786202

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