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Hemochromatosis type 3(HFE3)

MedGen UID:
388114
Concept ID:
C1858664
Disease or Syndrome
Synonyms: Hemochromatosis due to defect in transferrin receptor 2; Hereditary hemochromatosis type 3; HFE3; TFR2-Related Hereditary Hemochromatosis
SNOMED CT: Hemochromatosis type 3 (719974003); TFR2 (transferrin receptor 2 gene) related hemochromatosis (719974003)
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): TFR2 (7q22.1)
 
Monarch Initiative: MONDO:0011417
OMIM®: 604250
Orphanet: ORPHA225123

Disease characteristics

Excerpted from the GeneReview: TFR2-Related Hemochromatosis
TFR2-related hemochromatosis (TFR2-HC) is characterized by increased intestinal iron absorption resulting in iron accumulation in the liver, heart, pancreas, and endocrine organs. Age of onset is earlier than in HFE-related hemochromatosis. The majority of individuals present with signs and symptoms of iron overload in the third decade (e.g., weakness, fatigue, abdominal pain, hepatomegaly, arthritis, arthralgia, and progressive increase in skin pigmentation). Others present as young adults with nonspecific symptoms and abnormal serum iron studies or as adults with abnormal serum iron studies and signs of organ involvement including cirrhosis, diabetes mellitus, arthropathy, hypogonadism, cardiomyopathy, and increase in skin pigmentation. [from GeneReviews]
Authors:
Marco De Gobbi  |  Antonella Roetto   view full author information

Clinical features

From HPO
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Amenorrhea
MedGen UID:
8016
Concept ID:
C0002453
Finding
Absence of menses for an interval of time equivalent to a total of more than (or equal to) 3 previous cycles or 6 months.
Impotence
MedGen UID:
1720680
Concept ID:
CN208474
Finding
Inability to develop or maintain an erection of the penis.
Cardiomyopathy
MedGen UID:
209232
Concept ID:
C0878544
Disease or Syndrome
A myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease sufficient to cause the observed myocardial abnormality.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Arthritis
MedGen UID:
2043
Concept ID:
C0003864
Disease or Syndrome
Inflammation of a joint.
Lymphopenia
MedGen UID:
7418
Concept ID:
C0024312
Disease or Syndrome
A reduced number of lymphocytes in the blood.
Neutropenia
MedGen UID:
163121
Concept ID:
C0853697
Finding
An abnormally low number of neutrophils in the peripheral blood.
Increased circulating iron concentration
MedGen UID:
57739
Concept ID:
C0151900
Finding
The concentration of iron in the blood circulation is above the upper limit of normal.
Increased circulating ferritin concentration
MedGen UID:
69130
Concept ID:
C0241013
Finding
Increased concentration of ferritin in the blood circulation.
Elevated circulating hepatic transaminase concentration
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Elevated transferrin saturation
MedGen UID:
868498
Concept ID:
C4022892
Finding
An above normal level of saturation of serum transferrin with iron.
Purpura
MedGen UID:
19584
Concept ID:
C0034150
Disease or Syndrome
Purpura (from Latin
Hyperpigmentation of the skin
MedGen UID:
57992
Concept ID:
C0162834
Pathologic Function
A darkening of the skin related to an increase in melanin production and deposition.
Hypogonadotropic hypogonadism
MedGen UID:
82883
Concept ID:
C0271623
Disease or Syndrome
Hypogonadotropic hypogonadism is characterized by reduced function of the gonads (testes in males or ovaries in females) and results from the absence of the gonadal stimulating pituitary hormones

Recent clinical studies

Diagnosis

Khayat AA, Suchi M, Vitola B
J Pediatr Gastroenterol Nutr 2019 Apr;68(4):e68-e70. doi: 10.1097/MPG.0000000000002078. PMID: 29985876
Peters TM, Meulders AF, Redert K, Cuijpers ML, Rennings AJ, Janssen MC, Blijlevens NM, Swinkels DW
Neth J Med 2017 Mar;75(2):56-64. PMID: 28276324
Brissot P, Troadec MB, Bardou-Jacquet E, Le Lan C, Jouanolle AM, Deugnier Y, Loréal O
Blood Rev 2008 Jul;22(4):195-210. Epub 2008 Apr 21 doi: 10.1016/j.blre.2008.03.001. PMID: 18430498
Roetto A, Daraio F, Alberti F, Porporato P, Calì A, De Gobbi M, Camaschella C
Blood Cells Mol Dis 2002 Nov-Dec;29(3):465-70. doi: 10.1006/bcmd.2002.0585. PMID: 12547237
Roetto A, Totaro A, Piperno A, Piga A, Longo F, Garozzo G, Calì A, De Gobbi M, Gasparini P, Camaschella C
Blood 2001 May 1;97(9):2555-60. doi: 10.1182/blood.v97.9.2555. PMID: 11313241

Therapy

Brissot P, Troadec MB, Bardou-Jacquet E, Le Lan C, Jouanolle AM, Deugnier Y, Loréal O
Blood Rev 2008 Jul;22(4):195-210. Epub 2008 Apr 21 doi: 10.1016/j.blre.2008.03.001. PMID: 18430498

Prognosis

Hamada Y, Hirano E, Sugimoto K, Hanada K, Kaku T, Manda N, Tsuchida K
J Med Case Rep 2022 Jan 23;16(1):26. doi: 10.1186/s13256-021-03230-5. PMID: 35065677Free PMC Article
Ponka P
Semin Hematol 2002 Oct;39(4):249-62. doi: 10.1053/shem.2002.35638. PMID: 12382200

Clinical prediction guides

Calzolari A, Oliviero I, Deaglio S, Mariani G, Biffoni M, Sposi NM, Malavasi F, Peschle C, Testa U
Blood Cells Mol Dis 2007 Jul-Aug;39(1):82-91. Epub 2007 Apr 10 doi: 10.1016/j.bcmd.2007.02.003. PMID: 17428703
Frank J, Poblete-Gutiérrez P, Weiskirchen R, Gressner O, Merk HF, Lammert F
Physiol Res 2006;55 Suppl 2:S75-83. doi: 10.33549/physiolres.930000.55.S2.75. PMID: 17298224
Ponka P
Semin Hematol 2002 Oct;39(4):249-62. doi: 10.1053/shem.2002.35638. PMID: 12382200
Papanikolaou G, Politou M, Roetto A, Bosio S, Sakelaropoulos N, Camaschella C, Loukopoulos D
Blood Cells Mol Dis 2001 Jul-Aug;27(4):744-9. doi: 10.1006/bcmd.2001.0444. PMID: 11778658

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