MCID: IRN004
MIFTS: 42

Iron-Refractory Iron Deficiency Anemia

Categories: Genetic diseases, Rare diseases, Metabolic diseases, Blood diseases

Aliases & Classifications for Iron-Refractory Iron Deficiency Anemia

MalaCards integrated aliases for Iron-Refractory Iron Deficiency Anemia:

Name: Iron-Refractory Iron Deficiency Anemia 53 49 24 55 71 36 13 69
Irida 53 49 24 71
Anemia, Hypochromic Microcytic, with Defect in Iron Metabolism 53 49 24
Iron-Handling Disorder, Hereditary 53 49 24
Pseudo-Iron-Deficiency Anemia 53 49 71
Irida Syndrome 49 24 55
Hypochromic Microcytic Anemia with Defect in Iron Metabolism 71
Hereditary Iron-Handling Disorder 71

Characteristics:

Orphanet epidemiological data:

55
irida syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
autosomal recessive


HPO:

31
iron-refractory iron deficiency anemia:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 53 206200
Orphanet 55 ORPHA209981
UMLS via Orphanet 70 C0085576
ICD10 via Orphanet 33 D50.8
MedGen 39 C0085576
KEGG 36 H01278

Summaries for Iron-Refractory Iron Deficiency Anemia

NIH Rare Diseases : 49 Iron-refractory iron deficiency anemia (IRIDA) is a type of iron deficiency anemia that typically does not improve with oral iron treatment. Children with IRIDA have too little iron in their blood, which causes their red blood cells to be small (microcytic) and pale (hypochromic). The anemia tends to be mild to moderate, but without enough healthy red blood cells, different parts of the body do not get enough oxygen. Symptoms of IRIDA are usually mild, but may include pale skin and in some cases, feeling weak, tired, or dizzy. Growth and development of a child with IRIDA is usually normal. IRIDA is caused by changes or mutations in the TMPRSS6 gene and inheritance is autosomal recessive. IRIDA is usually suspected in childhood due to the results of routine blood tests, but the diagnosis is confirmed by genetic testing. Depending on the genetic change, some children may have enough improvement with oral iron treatment with vitamin C to need no other treatment. Therefore, treatment may first involve a trial of oral iron along with vitamin C for several weeks. If there is little to no improvement, treatment usually involves intravenous (IV) iron therapy, which may partially improve the anemia. Red blood cell levels often increase on their own in adulthood, so that the anemia no longer is a problem. Last updated: 11/27/2017

MalaCards based summary : Iron-Refractory Iron Deficiency Anemia, also known as irida, is related to microcytic anemia and iron metabolism disease, and has symptoms including intellectual disability, ichthyosis and pallor. An important gene associated with Iron-Refractory Iron Deficiency Anemia is TMPRSS6 (Transmembrane Protease, Serine 6), and among its related pathways/superpathways is Hfe effect on hepcidin production. The drugs Iron and Citric Acid have been mentioned in the context of this disorder. Affiliated tissues include skin and testes, and related phenotype is liver/biliary system.

OMIM : 53 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. (206200)

UniProtKB/Swiss-Prot : 71 Iron-refractory iron deficiency anemia: Key features include congenital hypochromic microcytic anemia, very low mean corpuscular erythrocyte volume, 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.

Genetics Home Reference : 24 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.

Related Diseases for Iron-Refractory Iron Deficiency Anemia

Diseases related to Iron-Refractory Iron Deficiency Anemia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 microcytic anemia 31.6 EPO TMPRSS6
2 iron metabolism disease 30.3 EPO HFE2
3 iron deficiency anemia 29.8 EPO HFE2 TMPRSS6
4 deficiency anemia 29.8 EPO HFE2 TMPRSS6
5 renal cell carcinoma, nonpapillary 10.0
6 essential thrombocythemia 10.0
7 hemochromatosis, type 1 9.5 HFE2 TMPRSS6

Graphical network of the top 20 diseases related to Iron-Refractory Iron Deficiency Anemia:



Diseases related to Iron-Refractory Iron Deficiency Anemia

Symptoms & Phenotypes for Iron-Refractory Iron Deficiency Anemia

Symptoms via clinical synopsis from OMIM:

53
Abdomen Gastroin testinal:
iron malabsorption

Laboratory Abnormalities:
inappropriately normal or increased plasma hepcidin

Hematology:
anemia, hypochromic microcytic
anemia, unresponsive to oral iron and only partially responsive to parenteral iron


Clinical features from OMIM:

206200

Human phenotypes related to Iron-Refractory Iron Deficiency Anemia:

55 31 (show all 11)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 55 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 ichthyosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0008064
3 pallor 55 31 hallmark (90%) Very frequent (99-80%) HP:0000980
4 hyperkeratosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0000962
5 peripheral neuropathy 55 31 hallmark (90%) Very frequent (99-80%) HP:0009830
6 abnormality of the intestine 55 31 hallmark (90%) Very frequent (99-80%) HP:0002242
7 intrahepatic cholestasis 55 31 frequent (33%) Frequent (79-30%) HP:0001406
8 hypocupremia 55 31 frequent (33%) Frequent (79-30%) HP:0011967
9 poikilocytosis 31 HP:0004447
10 anisocytosis 31 HP:0011273
11 hypochromic microcytic anemia 31 HP:0004840

MGI Mouse Phenotypes related to Iron-Refractory Iron Deficiency Anemia:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 liver/biliary system MP:0005370 8.8 TMPRSS6 EPO HFE2

Drugs & Therapeutics for Iron-Refractory Iron Deficiency Anemia

Drugs for Iron-Refractory Iron Deficiency Anemia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 10)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Iron Approved Phase 2 7439-89-6 23925
2
Citric Acid Approved, Nutraceutical, Vet_approved Phase 2 77-92-9 311
3 Anticoagulants Phase 2
4 Calcium, Dietary Phase 2
5 Chelating Agents Phase 2
6 Micronutrients Phase 2
7 Pharmaceutical Solutions Phase 2
8 Trace Elements Phase 2
9 Citrate Nutraceutical Phase 2
10 Iron Supplement Nutraceutical Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Triferic IRIDA Protocol Active, not recruiting NCT02905981 Phase 2 Fer-In-Sol;Shohl's solution;Triferic
2 Detection of β Thalassemia Carriers by Red Cell Parameters Obtained From the H2 Automatic Counter Enrolling by invitation NCT00481221
3 The Effect of Genetic Variation in TMPRSS6 Gene (SNP rs855791) on Oral Iron Absorption: an Iron Stable Isotope Study Not yet recruiting NCT03317873

Search NIH Clinical Center for Iron-Refractory Iron Deficiency Anemia

Genetic Tests for Iron-Refractory Iron Deficiency Anemia

Anatomical Context for Iron-Refractory Iron Deficiency Anemia

MalaCards organs/tissues related to Iron-Refractory Iron Deficiency Anemia:

38
Skin, Testes

Publications for Iron-Refractory Iron Deficiency Anemia

Articles related to Iron-Refractory Iron Deficiency Anemia:

(show all 24)
# Title Authors Year
1
Two novel mutations in TMPRSS6 associated with iron-refractory iron deficiency anemia in a mother and child. ( 28460265 )
2017
2
Iron Refractory Iron Deficiency Anemia in Dizygotic Twins Due to a Novel TMPRSS6 Gene Mutation in Addition to Polymorphisms Associated With High Susceptibility to Develop Ferropenic Anemia. ( 28491880 )
2017
3
Coexistence of Essential Thrombocythemia, Iron-Refractory Iron Deficiency Anemia and Renal Cell Carcinoma. ( 27103977 )
2016
4
Iron Refractory Iron Deficiency Anemia (IRIDA): A heterogeneous disease that is not always iron refractory. ( 27643674 )
2016
5
Response to parenteral iron therapy distinguish unexplained refractory iron deficiency anemia from iron-refractory iron deficiency anemia. ( 26818204 )
2016
6
Iron-Refractory Iron Deficiency Anemia May Not Lead to Neurocognitive Dysfunction: A Case Report. ( 27365303 )
2016
7
Iron-refractory iron deficiency anemia (IRIDA) cases with 2 novel TMPRSS6 mutations. ( 27120435 )
2016
8
Functional analysis of matriptase-2 mutations and domains: insights into the molecular basis of iron-refractory iron deficiency anemia. ( 25588876 )
2015
9
Iron-Refractory Iron Deficiency Anemia. ( 25805669 )
2015
10
Iron-refractory iron deficiency anemia (IRIDA). ( 25064705 )
2014
11
Novel mutation in the TMPRSS6 gene with iron-refractory iron deficiency anemia. ( 25252070 )
2014
12
Functional and clinical impact of novel tmprss6 variants in iron-refractory iron-deficiency anemia patients and genotype-phenotype studies. ( 25156943 )
2014
13
Administration of recombinant erythropoietin alone does not improve the phenotype in iron refractory iron deficiency anemia patients. ( 23180434 )
2013
14
Responsiveness to Parenteral Iron Therapy in Children with Oral Iron-Refractory Iron-Deficiency Anemia. ( 24087940 )
2013
15
Iron refractory iron deficiency anemia. ( 23729726 )
2013
16
Iron refractory iron deficiency anemia: presentation with hyperferritinemia and response to oral iron therapy. ( 23319530 )
2013
17
A novel mutation Gly603Arg of TMPRSS6 in a Korean female with iron- refractory iron deficiency anemia. ( 21618415 )
2012
18
Novel missense mutation in the TMPRSS6 gene in a Japanese female with iron-refractory iron deficiency anemia. ( 21643693 )
2011
19
Novel TMPRSS6 mutations associated with iron-refractory iron deficiency anemia (IRIDA). ( 20232450 )
2010
20
Iron-refractory iron deficiency anemia: new molecular mechanisms. ( 19776721 )
2009
21
Iron-refractory iron deficiency anemia. ( 19786206 )
2009
22
Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia. ( 19357398 )
2009
23
Matriptase-2 mutations in iron-refractory iron deficiency anemia patients provide new insights into protease activation mechanisms. ( 19592582 )
2009
24
Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). ( 18408718 )
2008

Variations for Iron-Refractory Iron Deficiency Anemia

UniProtKB/Swiss-Prot genetic disease variations for Iron-Refractory Iron Deficiency Anemia:

71 (show all 25)
# Symbol AA change Variation ID SNP ID
1 TMPRSS6 p.Gly442Arg VAR_044435 rs137853119
2 TMPRSS6 p.Asp521Asn VAR_044436 rs137853120
3 TMPRSS6 p.Arg774Cys VAR_044437 rs776069764
4 TMPRSS6 p.Tyr141Cys VAR_064075
5 TMPRSS6 p.Ile212Thr VAR_064076 rs776877803
6 TMPRSS6 p.Arg271Gln VAR_064077 rs776180387
7 TMPRSS6 p.Ser304Leu VAR_064078
8 TMPRSS6 p.Cys510Ser VAR_064079
9 TMPRSS6 p.Glu114Lys VAR_068665 rs199474803
10 TMPRSS6 p.Ala118Asp VAR_068666 rs267607121
11 TMPRSS6 p.Leu235Pro VAR_068668 rs199474802
12 TMPRSS6 p.Tyr418Cys VAR_068669 rs199474804
13 TMPRSS6 p.Glu522Lys VAR_068671 rs387907018
14 TMPRSS6 p.Gly603Arg VAR_068672 rs769083817
15 TMPRSS6 p.Pro765Ala VAR_068674 rs199474805
16 TMPRSS6 p.Trp247Cys VAR_072901
17 TMPRSS6 p.Thr287Asn VAR_072902
18 TMPRSS6 p.Cys335Phe VAR_072903
19 TMPRSS6 p.Cys510Arg VAR_072904
20 TMPRSS6 p.Asp521Gly VAR_072905
21 TMPRSS6 p.Trp590Arg VAR_072906 rs770897887
22 TMPRSS6 p.Arg597Trp VAR_072907 rs773272073
23 TMPRSS6 p.Ala605Gly VAR_072908
24 TMPRSS6 p.Leu606Arg VAR_072909
25 TMPRSS6 p.Ser623Thr VAR_072910

ClinVar genetic disease variations for Iron-Refractory Iron Deficiency Anemia:

6 (show all 13)
# Gene Variation Type Significance SNP ID Assembly Location
1 TMPRSS6 NM_153609.3(TMPRSS6): c.1564G> A (p.Glu522Lys) single nucleotide variant Pathogenic rs387907018 GRCh37 Chromosome 22, 37469590: 37469590
2 TMPRSS6 NM_153609.3(TMPRSS6): c.1904_1905dupGC (p.Lys636Alafs) duplication Pathogenic rs869320724 GRCh38 Chromosome 22, 37069308: 37069309
3 TMPRSS6 NM_153609.3(TMPRSS6): c.1813delG (p.Ala605Profs) deletion Pathogenic rs786205057 GRCh38 Chromosome 22, 37070539: 37070539
4 TMPRSS6 NM_153609.3(TMPRSS6): c.1582+1G> A single nucleotide variant Pathogenic rs786205058 GRCh38 Chromosome 22, 37073531: 37073531
5 TMPRSS6 NM_153609.3(TMPRSS6): c.2140+1G> C single nucleotide variant Pathogenic rs786205059 GRCh37 Chromosome 22, 37465112: 37465112
6 TMPRSS6 NM_153609.3(TMPRSS6): c.1324G> A (p.Gly442Arg) single nucleotide variant Pathogenic rs137853119 GRCh37 Chromosome 22, 37471220: 37471220
7 TMPRSS6 NM_153609.3(TMPRSS6): c.1561G> A (p.Asp521Asn) single nucleotide variant Pathogenic rs137853120 GRCh37 Chromosome 22, 37469593: 37469593
8 TMPRSS6 NM_153609.3(TMPRSS6): c.1065C> A (p.Tyr355Ter) single nucleotide variant Pathogenic rs137853121 GRCh37 Chromosome 22, 37480815: 37480815
9 TMPRSS6 TMPRSS6, 1-BP DEL, 1383A deletion Pathogenic
10 TMPRSS6 NM_153609.3(TMPRSS6): c.1179T> G (p.Tyr393Ter) single nucleotide variant Pathogenic rs137853122 GRCh37 Chromosome 22, 37480379: 37480379
11 TMPRSS6 NM_153609.3(TMPRSS6): c.1795C> T (p.Arg599Ter) single nucleotide variant Pathogenic rs137853123 GRCh37 Chromosome 22, 37466597: 37466597
12 TMPRSS6 NM_153609.3(TMPRSS6): c.2055_2058dupCCCC (p.Val687Profs) duplication Pathogenic rs786205060 GRCh38 Chromosome 22, 37069155: 37069158
13 TMPRSS6 NM_153609.3(TMPRSS6): c.353C> A (p.Ala118Asp) single nucleotide variant Pathogenic rs267607121 GRCh37 Chromosome 22, 37494466: 37494466

Expression for Iron-Refractory Iron Deficiency Anemia

Search GEO for disease gene expression data for Iron-Refractory Iron Deficiency Anemia.

Pathways for Iron-Refractory Iron Deficiency Anemia

Pathways related to Iron-Refractory Iron Deficiency Anemia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 9.47 HFE2 TMPRSS6

GO Terms for Iron-Refractory Iron Deficiency Anemia

Biological processes related to Iron-Refractory Iron Deficiency Anemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of transcription by RNA polymerase II GO:0000122 9.43 EPO HFE2 TMPRSS6
2 cellular iron ion homeostasis GO:0006879 9.16 HFE2 TMPRSS6
3 negative regulation of BMP signaling pathway GO:0030514 8.96 HFE2 TMPRSS6
4 iron ion homeostasis GO:0055072 8.62 HFE2 TMPRSS6

Molecular functions related to Iron-Refractory Iron Deficiency Anemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 serine-type endopeptidase activity GO:0004252 8.96 TMPRSS11A TMPRSS6
2 serine-type peptidase activity GO:0008236 8.62 TMPRSS11A TMPRSS6

Sources for Iron-Refractory Iron Deficiency Anemia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
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29 HGMD
30 HMDB
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32 ICD10
33 ICD10 via Orphanet
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35 IUPHAR
36 KEGG
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42 MESH via Orphanet
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58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
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70 UMLS via Orphanet
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