U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Hemochromatosis type 1(HFE1)

MedGen UID:
854011
Concept ID:
C3469186
Disease or Syndrome
Synonyms: HFE-Associated Hereditary Hemochromatosis; HFE1
SNOMED CT: Hemochromatosis type 1 (1186847009); HFE related hemochromatosis (1186847009)
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).
 
Genes (locations): BMP2 (20p12.3); HFE (6p22.2)
 
Monarch Initiative: MONDO:0021001
OMIM®: 235200
Orphanet: ORPHA465508

Disease characteristics

Excerpted from the GeneReview: HFE Hemochromatosis
HFE hemochromatosis is characterized by inappropriately high absorption of iron by the small intestinal mucosa. The phenotypic spectrum of HFE hemochromatosis includes: Persons with clinical HFE hemochromatosis, in whom manifestations of end-organ damage secondary to iron overload are present; Individuals with biochemical HFE hemochromatosis, in whom transferrin-iron saturation is increased and the only evidence of iron overload is increased serum ferritin concentration; and Non-expressing p.Cys282Tyr homozygotes, in whom neither clinical manifestations of HFE hemochromatosis nor iron overload are present. Clinical HFE hemochromatosis is characterized by excessive storage of iron in the liver, skin, pancreas, heart, joints, and anterior pituitary gland. In untreated individuals, early symptoms include: abdominal pain, weakness, lethargy, weight loss, arthralgias, diabetes mellitus; and increased risk of cirrhosis when the serum ferritin is higher than 1,000 ng/mL. Other findings may include progressive increase in skin pigmentation, congestive heart failure, and/or arrhythmias, arthritis, and hypogonadism. Clinical HFE hemochromatosis is more common in men than women. [from GeneReviews]
Authors:
James C Barton  |  Corwin Q Edwards   view full author information

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
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.
Azoospermia
MedGen UID:
2150
Concept ID:
C0004509
Disease or Syndrome
Absence of any measurable level of sperm,whereby spermatozoa cannot be observed even after centrifugation of the semen pellet.
Testicular atrophy
MedGen UID:
57626
Concept ID:
C0156312
Disease or Syndrome
Wasting (atrophy) of the testicle (the male gonad) manifested by a decrease in size and potentially by a loss of fertility.
Impotence
MedGen UID:
1720680
Concept ID:
CN208474
Finding
Inability to develop or maintain an erection of the penis.
Cardiac arrhythmia
MedGen UID:
2039
Concept ID:
C0003811
Finding
Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both.
Cardiomegaly
MedGen UID:
5459
Concept ID:
C0018800
Finding
Increased size of the heart, clinically defined as an increased transverse diameter of the cardiac silhouette that is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography.
Congestive heart failure
MedGen UID:
9169
Concept ID:
C0018802
Disease or Syndrome
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
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.
Ascites
MedGen UID:
416
Concept ID:
C0003962
Disease or Syndrome
Accumulation of fluid in the peritoneal cavity.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
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.
Hepatocellular carcinoma
MedGen UID:
389187
Concept ID:
C2239176
Neoplastic Process
Hepatocellular carcinoma is the major histologic type of malignant primary liver neoplasm. It is the fifth most common cancer and the third most common cause of death from cancer worldwide. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Hepatoblastomas comprise 1 to 2% of all malignant neoplasms of childhood, most often occurring in children under 3 years of age. Hepatoblastomas are thought to be derived from undifferentiated hepatocytes (Taniguchi et al., 2002).
Arthropathy
MedGen UID:
7190
Concept ID:
C0022408
Disease or Syndrome
Any disorder of the joints.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Pleural effusion
MedGen UID:
10805
Concept ID:
C0032227
Disease or Syndrome
The presence of an excessive amount of fluid in the pleural cavity.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
A group of abnormalities characterized by hyperglycemia and glucose intolerance.
Increased serum iron
MedGen UID:
57739
Concept ID:
C0151900
Finding
Increased circulating ferritin concentration
MedGen UID:
69130
Concept ID:
C0241013
Finding
Increased concentration of ferritin in the blood circulation.
Glucose intolerance
MedGen UID:
75760
Concept ID:
C0271650
Disease or Syndrome
Glucose intolerance (GI) can be defined as dysglycemia that comprises both prediabetes and diabetes. It includes the conditions of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and diabetes mellitus (DM).
Elevated hepatic transaminase
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.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.
Telangiectasia
MedGen UID:
21088
Concept ID:
C0039446
Finding
Telangiectasias refer to small dilated blood vessels located near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. Telangiectasia are located especially on the tongue, lips, palate, fingers, face, conjunctiva, trunk, nail beds, and fingertips.
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

Professional guidelines

PubMed

Savatt JM, Johns A, Schwartz MLB, McDonald WS, Salvati ZM, Oritz NM, Masnick M, Hatchell K, Hao J, Buchanan AH, Williams MS
JAMA Netw Open 2023 Oct 2;6(10):e2338995. doi: 10.1001/jamanetworkopen.2023.38995. PMID: 37870835Free PMC Article
Camacho A, Funck-Brentano T, Simão M, Cancela L, Ottaviani S, Cohen-Solal M, Richette P
PLoS One 2015;10(3):e0122817. Epub 2015 Mar 30 doi: 10.1371/journal.pone.0122817. PMID: 25822977Free PMC Article

Curated

Stuhrmann M, Gabriel H, Keeney S
Eur J Hum Genet 2010 Sep;18(9) Epub 2010 Feb 3 doi: 10.1038/ejhg.2009.245. PMID: 20125190Free PMC Article

Recent clinical studies

Etiology

Urbina MT, Benjamin I, Medina R, Jiménez J, Trías L, Lerner J
JBRA Assist Reprod 2017 Dec 1;21(4):356-360. doi: 10.5935/1518-0557.20170062. PMID: 29099150Free PMC Article
Camacho A, Funck-Brentano T, Simão M, Cancela L, Ottaviani S, Cohen-Solal M, Richette P
PLoS One 2015;10(3):e0122817. Epub 2015 Mar 30 doi: 10.1371/journal.pone.0122817. PMID: 25822977Free PMC Article
Cruz-Rojo J, Fontanellas A, Morán-Jiménez MJ, Navarro-Ordóñez S, García-Bravo M, Méndez M, Muñoz-Rivero MC, de Salamanca RE
Cell Mol Biol (Noisy-le-grand) 2002 Dec;48(8):845-52. PMID: 12699242

Diagnosis

Savatt JM, Johns A, Schwartz MLB, McDonald WS, Salvati ZM, Oritz NM, Masnick M, Hatchell K, Hao J, Buchanan AH, Williams MS
JAMA Netw Open 2023 Oct 2;6(10):e2338995. doi: 10.1001/jamanetworkopen.2023.38995. PMID: 37870835Free PMC Article
Camacho A, Funck-Brentano T, Simão M, Cancela L, Ottaviani S, Cohen-Solal M, Richette P
PLoS One 2015;10(3):e0122817. Epub 2015 Mar 30 doi: 10.1371/journal.pone.0122817. PMID: 25822977Free PMC Article
Hulihan MM, Sayers CA, Grosse SD, Garrison C, Grant AM
Am J Prev Med 2011 Dec;41(6 Suppl 4):S422-7. doi: 10.1016/j.amepre.2011.09.020. PMID: 22099368
Kaczorowska-Hac B, Sikorska K, Bielawski KP, Schramm K, Balcerska A
Int J Hematol 2007 May;85(4):300-3. doi: 10.1532/IJH97.E0605. PMID: 17483072
Cruz-Rojo J, Fontanellas A, Morán-Jiménez MJ, Navarro-Ordóñez S, García-Bravo M, Méndez M, Muñoz-Rivero MC, de Salamanca RE
Cell Mol Biol (Noisy-le-grand) 2002 Dec;48(8):845-52. PMID: 12699242

Prognosis

Ponka P
Semin Hematol 2002 Oct;39(4):249-62. doi: 10.1053/shem.2002.35638. PMID: 12382200

Clinical prediction guides

Savatt JM, Johns A, Schwartz MLB, McDonald WS, Salvati ZM, Oritz NM, Masnick M, Hatchell K, Hao J, Buchanan AH, Williams MS
JAMA Netw Open 2023 Oct 2;6(10):e2338995. doi: 10.1001/jamanetworkopen.2023.38995. PMID: 37870835Free PMC Article
Sousa L, Garcia IJ, Costa TG, Silva LN, Renó CO, Oliveira ES, Tilelli CQ, Santos LL, Cortes VF, Santos HL, Barbosa LA
PLoS One 2015;10(7):e0132852. Epub 2015 Jul 21 doi: 10.1371/journal.pone.0132852. PMID: 26197432Free PMC Article
Kaczorowska-Hac B, Sikorska K, Bielawski KP, Schramm K, Balcerska A
Int J Hematol 2007 May;85(4):300-3. doi: 10.1532/IJH97.E0605. PMID: 17483072
Vaiopoulos G, Papanikolaou G, Politou M, Jibreel I, Sakellaropoulos N, Loukopoulos D
Arthritis Rheum 2003 Jan;48(1):227-30. doi: 10.1002/art.10755. PMID: 12528123
Ponka P
Semin Hematol 2002 Oct;39(4):249-62. doi: 10.1053/shem.2002.35638. PMID: 12382200

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...