MCID: HMC010
MIFTS: 42

Hemochromatosis, Type 3

Categories: Genetic diseases, Rare diseases, Liver diseases, Metabolic diseases

Aliases & Classifications for Hemochromatosis, Type 3

MalaCards integrated aliases for Hemochromatosis, Type 3:

Name: Hemochromatosis, Type 3 53 13 51 41 69
Hemochromatosis Type 3 12 72 49 55 28
Hemochromatosis Due to Defect in Transferrin Receptor 2 53 12 49 71
Hfe3 53 12 49 71
Tfr2-Related Hemochromatosis 12 55
Hemochromatosis 3 71

Characteristics:

Orphanet epidemiological data:

55
hemochromatosis type 3
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Adult;

OMIM:

53
Inheritance:
autosomal recessive


HPO:

31
hemochromatosis, type 3:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 53 604250
Disease Ontology 12 DOID:0111030
ICD10 32 E83.1
Orphanet 55 ORPHA225123
MESH via Orphanet 42 C537248
UMLS via Orphanet 70 C1858664
ICD10 via Orphanet 33 E83.1
MedGen 39 C1858664
UMLS 69 C1858664

Summaries for Hemochromatosis, Type 3

NIH Rare Diseases : 49 Hemochromatosis type 3 is a disease in which too much iron builds up in the body. This is also called iron overload. Accumulation of iron in the organs is toxic and can cause organ damage. While many organs can be affected, iron overload is especially likely to affect the liver, heart, and pancreas. Early symptoms of hemochromatosis type 3 can include fatigue, weakness, and joint pain. Other symptoms may include abdominal pain, loss of sex drive, liver disease, diabetes, heart problems, and skin discoloration. Symptoms of hemochromatosis type 3 typically begin before 30-years-old. Hemochromatosis type 3 is caused by genetic changes (mutations or pathogenic variants) to the TFR2 gene. The disease is inherited in an autosomal recessive manner. A diagnosis of hemochromatosis type 3 is suspected when a doctor observes signs and symptoms of the disease. A doctor may decide to order laboratory tests including a liver biopsy, MRI, or blood test. The diagnosis can be confirmed with genetic testing. Treatment of hemochromatosis type 3 usually involves reducing iron levels by removing blood (phlebotomy) or iron chelation. These treatments can prevent additional organ damage but typically do not reverse existing damage. To learn more about other types of hemochromatosis click on the disease names below:Hemochromatosis type 1 Hemochromatosis type 2 Hemochromatosis type 4 Hemochromatosis type 5 Neonatal hemochromatosis Last updated: 2/15/2018

MalaCards based summary : Hemochromatosis, Type 3, also known as hemochromatosis type 3, is related to hemochromatosis type 2 and hemochromatosis, type 1, and has symptoms including fatigue, arthritis and anemia. An important gene associated with Hemochromatosis, Type 3 is TFR2 (Transferrin Receptor 2). The drugs Iron and Omeprazole have been mentioned in the context of this disorder. Affiliated tissues include liver, skin and heart.

Disease Ontology : 12 A hemochromatosis that has material basis in homozygous or compound heterozygous mutation in the TFR2 gene on chromosome 7q22.

UniProtKB/Swiss-Prot : 71 Hemochromatosis 3: A disorder of iron metabolism characterized by iron overload. Excess iron is deposited in a variety of organs leading to their failure, and resulting in serious illnesses including cirrhosis, hepatomas, diabetes, cardiomyopathy, arthritis, and hypogonadotropic hypogonadism. Severe effects of the disease usually do not appear until after decades of progressive iron loading.

Wikipedia : 72 Haemochromatosis type 3 is a type of Iron overload disorder associated with deficiencies in transferrin... more...

Description from OMIM: 604250

Related Diseases for Hemochromatosis, Type 3

Graphical network of the top 20 diseases related to Hemochromatosis, Type 3:



Diseases related to Hemochromatosis, Type 3

Symptoms & Phenotypes for Hemochromatosis, Type 3

Symptoms via clinical synopsis from OMIM:

53
Neurologic Behavioral Psychiatric Manifestations:
fatigue

Skeletal:
arthritis

Abdomen Liver:
cirrhosis
fibrosis

Genitourinary External Genitalia Male:
hypogonadism

Genitourinary Internal Genitalia Female:
amenorrhea

Endocrine Features:
diabetes

Genitourinary Internal Genitalia Male:
decreased libido
impotence

Hematology:
anemia
lymphopenia
neutropenia
thrombocytopenic purpura

Cardiovascular Heart:
cardiomyopathy

Laboratory Abnormalities:
increased serum ferritin
increased serum iron
increased transferrin saturation
increased liver transaminases

Skin Nails Hair Skin:
hyperpigmentation


Clinical features from OMIM:

604250

Human phenotypes related to Hemochromatosis, Type 3:

31 (show all 14)
# Description HPO Frequency HPO Source Accession
1 fatigue 31 HP:0012378
2 arthritis 31 HP:0001369
3 anemia 31 HP:0001903
4 elevated hepatic transaminases 31 HP:0002910
5 cirrhosis 31 HP:0001394
6 cardiomyopathy 31 HP:0001638
7 hypogonadotrophic hypogonadism 31 HP:0000044
8 lymphopenia 31 HP:0001888
9 neutropenia 31 HP:0001875
10 impotence 31 HP:0000802
11 increased serum ferritin 31 HP:0003281
12 increased serum iron 31 HP:0003452
13 hyperpigmentation of the skin 31 HP:0000953
14 amenorrhea 31 HP:0000141

UMLS symptoms related to Hemochromatosis, Type 3:


fatigue

Drugs & Therapeutics for Hemochromatosis, Type 3

Drugs for Hemochromatosis, Type 3 (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 42)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Iron Approved Phase 4,Phase 3,Phase 2,Phase 1 7439-89-6 23925
2
Omeprazole Approved, Investigational, Vet_approved Phase 4 73590-58-6 4594
3
Deferasirox Approved, Investigational Phase 4,Phase 1,Phase 2 201530-41-8 5493381
4
Deferoxamine Approved, Investigational Phase 4,Phase 3,Phase 2 70-51-9 2973
5
Deferiprone Approved Phase 4,Phase 3,Phase 2,Phase 1 30652-11-0 2972
6 Antacids Phase 4
7 Anti-Ulcer Agents Phase 4
8 Gastrointestinal Agents Phase 4
9 Proton pump inhibitors Phase 4
10 Chelating Agents Phase 4,Phase 3,Phase 2,Phase 1
11 Iron Chelating Agents Phase 4,Phase 3,Phase 2,Phase 1
12 Liver Extracts Phase 4,Phase 2
13
Ethanol Approved Phase 3 64-17-5 702
14
Hydroxyurea Approved Phase 3 127-07-1 3657
15 Pharmaceutical Solutions Phase 2, Phase 3
16 Nucleic Acid Synthesis Inhibitors Phase 3
17
Cholecalciferol Approved, Nutraceutical Phase 2 67-97-0 10883523 5280795 6221
18
Ergocalciferol Approved, Nutraceutical Phase 2 50-14-6 5280793
19
Vitamin D Approved, Nutraceutical, Vet_approved Phase 2 1406-16-2
20 Micronutrients Phase 2,Phase 1
21 Trace Elements Phase 2,Phase 1
22 Hepcidins Phase 2
23 Calcium, Dietary Phase 2,Phase 1
24 Antirheumatic Agents Phase 2
25 Interleukin 1 Receptor Antagonist Protein Phase 2
26 Anti-Infective Agents Phase 2
27 Vaccines Phase 1, Phase 2
28 Bone Density Conservation Agents Phase 2
29 Ergocalciferols Phase 2
30 Vitamins Phase 2
31 Calciferol Nutraceutical Phase 2
32 Vitamin D2 Nutraceutical Phase 2
33
Nifedipine Approved Phase 1 21829-25-4 4485
34 calcium channel blockers Phase 1
35 Tocolytic Agents Phase 1
36 Vasodilator Agents Phase 1
37
Pantoprazole Approved 102625-70-7 4679
38 Kava Approved, Investigational, Nutraceutical 9000-38-8
39 Trichostatin A
40 Hematinics
41
Bilirubin 635-65-4 5280352
42 Iron Supplement Nutraceutical

Interventional clinical trials:

(show top 50) (show all 55)

# Name Status NCT ID Phase Drugs
1 Evaluation of the Efficacy in Decreasing Iron Absorption in Patients With Congenital Dyserythropoietic Anemia Type I by Treatment With LOSEC Unknown status NCT01795794 Phase 4 omeprazole
2 Pilot Study for Patients With Poor Response to Deferasirox Completed NCT00749515 Phase 4 Deferoxamine;Deferasirox
3 Efficacy Study of the Use of Sequential DFP-DFO Versus DFP Completed NCT00733811 Phase 4 Deferiprone (DFP) and Deferoxamine (DFO);Deferiprone (DFP)
4 Erythrocytapheresis Versus Phlebotomy as Maintenance Therapy in Hereditary Hemochromatosis (HH) Patients Unknown status NCT01398644 Phase 3
5 Haemochromatosis:Phlebotomy Versus Erythrocytapheresis Therapy Completed NCT00202436 Phase 3
6 Clinical Management of Hereditary Hemochromatosis: Phlebotomy vs. Erythrocytoapheresis Completed NCT00440986 Phase 2, Phase 3
7 Study With Deferiprone and/or Desferrioxamine in Iron Overloaded Patients Completed NCT00350662 Phase 3 Deferiprone (L1);Desferrioxamine
8 Efficacy and Safety of the Iron Chelator Deferiprone in Parkinson's Disease Completed NCT00943748 Phase 2, Phase 3 deferiprone;placebo
9 Screening of Hepatocellular Carcinoma in Patients With Compensated Cirrhosis Completed NCT00190385 Phase 3
10 Stroke With Transfusions Changing to Hydroxyurea Terminated NCT00122980 Phase 3 Hydroxyurea
11 Safety and Efficacy of Deferasirox (ICL670) in Patients With Iron Overload Resulting From Hereditary Hemochromatosis Completed NCT00395629 Phase 1, Phase 2 Deferasirox (ICL670)
12 Study Using Deferiprone Alone or in Combination With Desferrioxamine in Iron Overloaded Transfusion-dependent Patients Completed NCT00349453 Phase 2 Deferiprone (L1);Deferiprone (L1);Desferrioxamine
13 Evaluation of Subcutaneous Desferrioxamine as Treatment for Transfusional Hemochromatosis Completed NCT00000595 Phase 2 deferoxamine
14 High-Tc Susceptometer to Monitor Transfusional Iron Overload Completed NCT01241357 Phase 2
15 Treatment of Refractory Hemochromatosis Rheumatism by Anakinra: a Preliminary Phase II Study Recruiting NCT02263638 Phase 2 Anakinra
16 A Study of LJPC-401 for the Treatment of Iron Overload in Adult Patients With Hereditary Hemochromatosis Recruiting NCT03395704 Phase 2 LJPC-401;Placebo
17 Analysis of the Modulation of Serum Hepcidin Level in Response to Iron Oral Intake: Potential Interest for the Differential Diagnosis Between Ferroportin Disease and Dysmetabolic Hepatosiderosis. Recruiting NCT01949467 Phase 2 iron fumarate
18 Trial of Therapeutic Vaccine in Patients With Cholangiocarcinoma Recruiting NCT03042182 Phase 1, Phase 2
19 A Two-year Study to Evaluate the Efficacy and Safety of Deferasirox Film-coated Tablet Versus Phlebotomy in Patients With Hereditary Hemochromatosis. Not yet recruiting NCT03203850 Phase 2 Deferasirox FCT
20 The Deferasirox-calcium-vitamin D3 Therapy for Postmenopausal Osteoporosis (PMOP) Not yet recruiting NCT02854722 Phase 2 Deferasirox and calcium-vitamin D3;Calcium-vitamin D3
21 Treatment of Iron Overload With Deferasirox (Exjade) in Hereditary Hemochromatosis and Myelodysplastic Syndrome Terminated NCT01892644 Phase 2 Deferasirox;Deferasirox
22 Oral Nifedipine to Treat Iron Overload Completed NCT00712738 Phase 1 Nifedipine
23 Implications for Quality of Life and Quality of Care in Patients With Hereditary Haemochromatosis Unknown status NCT01991925
24 Erythrocyte Apheresis Versus Phlebotomy in Hemochromatosis Unknown status NCT00509652
25 Proton Pump Inhibitors in the Prevention of Iron Reaccumulation in Patient With Hereditary Hemochromatosis Unknown status NCT01524757 Pantoprazole
26 Research Network for Neonatal Diseases Induced by Tissular Fetomaternal Alloimmunization Unknown status NCT00199628
27 Estimation of Myocardial Iron Overload by 3 Tesla MRI in HFE Hereditary Haemochromatosis Completed NCT02099214
28 HEPFER-Evaluation of a New Phenotypic Biological Marker in Genetic Type 1 Hemochromatosis Completed NCT01784939
29 Bone Status on Patients With Genetic Hemochromatosis: a 3 Years Descriptive and Evolutionary Study Completed NCT01556360
30 Respiratory Variations For Assessing Blood Withdrawal Completed NCT03066414
31 Deferoxamine for the Treatment of Hemochromatosis Completed NCT00001203
32 Evaluation of a New MR Pulse Sequence to Quantify Liver Iron Concentration Completed NCT00587535
33 Hemochromatosis--Genetic Prevalence and Penetrance Completed NCT00006312
34 Statistical Basis for Hemochromatosis Screening Completed NCT00005559
35 Hemochromatosis and Iron Overload Screening Study (HEIRS) Completed NCT00005541
36 Mi-iron - Moderately Increased Iron - is Reducing Iron Overload Necessary? Completed NCT01631708
37 Iron Overload in African Americans Completed NCT00001455
38 Impact of Host Iron Status and Iron Supplement Use on Erythrocytic Stage of Plasmodium Falciparum Completed NCT01027663
39 Study of the Pathogenesis of Porphyria Cutanea Tarda Completed NCT00005103
40 Risk Factors of Porphyria Cutanea Tarda (PCT) Completed NCT00213772
41 Ischemia Modified Albumin (IMA) Expression in the Male and Female Population Completed NCT02894671
42 Iron Overload in Stem Cell Transplant Recipients Completed NCT00806715
43 Treatment of Hemochromatosis Recruiting NCT00007150
44 Impact of Bloodletting on Iron Metabolism in Type 1 Hemochromatosis Recruiting NCT01810965
45 Transferrin Saturation and Asthenia in Hemochromatosis Recruiting NCT03356548
46 Confounder-Corrected Quantitative MRI Biomarker of Hepatic Iron Content Recruiting NCT02025543
47 Long Term Follow-up of Integra® Cadence™ Total Ankle System in Primary Ankle Joint Replacement Recruiting NCT03247023
48 China Registry for Genetic / Metabolic Liver Diseases Recruiting NCT03131427 Standard of care
49 Evaluation of Patients With Liver Disease Recruiting NCT00001971
50 The Nor-Hand Study Recruiting NCT03083548

Search NIH Clinical Center for Hemochromatosis, Type 3

Cochrane evidence based reviews: hemochromatosis, type 3

Genetic Tests for Hemochromatosis, Type 3

Genetic tests related to Hemochromatosis, Type 3:

# Genetic test Affiliating Genes
1 Hemochromatosis Type 3 28 TFR2

Anatomical Context for Hemochromatosis, Type 3

MalaCards organs/tissues related to Hemochromatosis, Type 3:

38
Liver, Skin, Heart, Testes, Pancreas, Bone

Publications for Hemochromatosis, Type 3

Articles related to Hemochromatosis, Type 3:

# Title Authors Year
1
Clinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene. ( 11984516 )
2002
2
New mutations inactivating transferrin 2 in hemochromatosis type 3. ( 11313241 )
2001

Variations for Hemochromatosis, Type 3

UniProtKB/Swiss-Prot genetic disease variations for Hemochromatosis, Type 3:

71
# Symbol AA change Variation ID SNP ID
1 TFR2 p.Met172Lys VAR_012738 rs80338879
2 TFR2 p.Val22Ile VAR_042515 rs80338876
3 TFR2 p.Gln690Pro VAR_042517 rs80338889

ClinVar genetic disease variations for Hemochromatosis, Type 3:

6 (show all 16)
# Gene Variation Type Significance SNP ID Assembly Location
1 TFR2 NM_003227.3(TFR2): c.1330G> A (p.Ala444Thr) single nucleotide variant Pathogenic rs80338884 GRCh38 Chromosome 7, 100629313: 100629313
2 TFR2 NM_003227.3(TFR2): c.1186C> T (p.Arg396Ter) single nucleotide variant Pathogenic rs80338882 GRCh37 Chromosome 7, 100228596: 100228596
3 TFR2 NM_003227.3(TFR2): c.1231_1233delAAC (p.Asn412del) deletion Pathogenic rs80338883 GRCh37 Chromosome 7, 100228549: 100228551
4 TFR2 NM_003227.3(TFR2): c.1469T> G (p.Leu490Arg) single nucleotide variant Pathogenic rs80338886 GRCh37 Chromosome 7, 100225851: 100225851
5 TFR2 NM_003227.3(TFR2): c.1665delC (p.Ser556Alafs) deletion Pathogenic rs80338887 GRCh37 Chromosome 7, 100225384: 100225384
6 TFR2 NM_003227.3(TFR2): c.1861_1872delGCCGTGGCCCAG (p.Ala621_Gln624del) deletion Pathogenic rs80338888 GRCh37 Chromosome 7, 100225010: 100225021
7 TFR2 NM_003227.3(TFR2): c.2137-1G> A single nucleotide variant Pathogenic rs80338890 GRCh37 Chromosome 7, 100218750: 100218750
8 TFR2 NM_003227.3(TFR2): c.2374G> A (p.Gly792Arg) single nucleotide variant Pathogenic/Likely pathogenic rs80338891 GRCh37 Chromosome 7, 100218512: 100218512
9 TFR2 NM_003227.3(TFR2): c.313C> T (p.Arg105Ter) single nucleotide variant Pathogenic rs80338878 GRCh37 Chromosome 7, 100238469: 100238469
10 TFR2 NM_003227.3(TFR2): c.64G> A (p.Val22Ile) single nucleotide variant Pathogenic rs80338876 GRCh37 Chromosome 7, 100238821: 100238821
11 TFR2 NM_003227.3(TFR2): c.949C> T (p.Gln317Ter) single nucleotide variant Pathogenic rs80338881 GRCh37 Chromosome 7, 100229722: 100229722
12 TFR2 NM_003227.3(TFR2): c.750C> G (p.Tyr250Ter) single nucleotide variant Pathogenic rs80338880 GRCh37 Chromosome 7, 100230723: 100230723
13 TFR2 NM_003227.3(TFR2): c.88_89insC (p.Arg30Profs) insertion Pathogenic rs80338877 GRCh37 Chromosome 7, 100238797: 100238797
14 TFR2 NM_003227.3(TFR2): c.515T> A (p.Met172Lys) single nucleotide variant Pathogenic rs80338879 GRCh37 Chromosome 7, 100231138: 100231138
15 TFR2 NM_003227.3(TFR2): c.1364G> A (p.Arg455Gln) single nucleotide variant risk factor rs41303501 GRCh37 Chromosome 7, 100226902: 100226902
16 TFR2 NM_003227.3(TFR2): c.2069A> C (p.Gln690Pro) single nucleotide variant Pathogenic rs80338889 GRCh37 Chromosome 7, 100224453: 100224453

Expression for Hemochromatosis, Type 3

Search GEO for disease gene expression data for Hemochromatosis, Type 3.

Pathways for Hemochromatosis, Type 3

GO Terms for Hemochromatosis, Type 3

Cellular components related to Hemochromatosis, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cytoplasmic vesicle GO:0031410 9.16 HFE TFR2
2 external side of plasma membrane GO:0009897 8.96 HFE TFR2
3 HFE-transferrin receptor complex GO:1990712 8.62 HFE TFR2

Biological processes related to Hemochromatosis, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular iron ion homeostasis GO:0006879 9.4 HFE TFR2
2 iron ion homeostasis GO:0055072 9.37 HFE TFR2
3 acute-phase response GO:0006953 9.32 HFE TFR2
4 transferrin transport GO:0033572 9.26 HFE TFR2
5 response to iron ion GO:0010039 9.16 HFE TFR2
6 positive regulation of peptide hormone secretion GO:0090277 8.96 HFE TFR2
7 cellular response to iron ion GO:0071281 8.62 HFE TFR2

Molecular functions related to Hemochromatosis, Type 3 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 co-receptor binding GO:0039706 8.62 HFE TFR2

Sources for Hemochromatosis, Type 3

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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