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Hemochromatosis type 1(HFE1)

MedGen UID:
140272
Concept ID:
C0392514
Disease or Syndrome
Synonyms: HFE-Associated Hereditary Hemochromatosis; HFE1
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, 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 homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
SNOMED CT: Idiopathic hemochromatosis (399053004); Primary hemochromatosis (399170009); Hereditary hemochromatosis (35400008); Primary hemochromatosis (35400008); Idiopathic hemochromatosis (35400008); Familial hemochromatosis (35400008)
 
Genes (locations): BMP2 (20p12.3); HFE (6p22.2)
OMIM®: 235200

Disease characteristics

Excerpted from the GeneReview: HFE-Associated Hereditary Hemochromatosis
HFE-associated hereditary hemochromatosis (HFE-HH) is characterized by inappropriately high absorption of iron by the gastrointestinal mucosa. The phenotypic spectrum of HFE-HH is now recognized to include: Those with clinical HFE-HH, in which manifestations of end-organ damage secondary to iron storage are present; Those with biochemical HFE-HH, in which the only evidence of iron overload is increased transferrin-iron saturation and increased serum ferritin concentration; Non-expressing p.Cys282Tyr homozygotes, in whom neither clinical manifestations of HFE-HH nor iron overload is present. Clinical HFE-HH is characterized by excessive storage of iron in the liver, skin, pancreas, heart, joints, and testes. In untreated individuals, early symptoms may include: abdominal pain, weakness, lethargy, and weight loss; the risk of cirrhosis is significantly increased when the serum ferritin is higher than 1,000 ng/mL; other findings may include progressive increase in skin pigmentation, diabetes mellitus, congestive heart failure, and/or arrhythmias, arthritis, and hypogonadism. Clinical HFE-HH is more common in men than women. [from GeneReviews]
Authors:
Rebecca Seckington  |  Lawrie Powell   view full author information

Additional description

From GHR
Hereditary hemochromatosis is a disorder that causes the body to absorb too much iron from the diet. The excess iron is stored in the body's tissues and organs, particularly the skin, heart, liver, pancreas, and joints. Because humans cannot increase the excretion of iron, excess iron can overload and eventually damage tissues and organs. For this reason, hereditary hemochromatosis is also called an iron overload disorder.Early symptoms of hereditary hemochromatosis are nonspecific and may include fatigue, joint pain, abdominal pain, and loss of sex drive. Later signs and symptoms can include arthritis, liver disease, diabetes, heart abnormalities, and skin discoloration. The appearance and progression of symptoms can be affected by environmental and lifestyle factors such as the amount of iron in the diet, alcohol use, and infections.Hereditary hemochromatosis is classified by type depending on the age of onset and other factors such as genetic cause and mode of inheritance. Type 1, the most common form of the disorder, and type 4 (also called ferroportin disease) begin in adulthood. Men with type 1 or type 4 hemochromatosis typically develop symptoms between the ages of 40 and 60, and women usually develop symptoms after menopause.Type 2 hemochromatosis is a juvenile-onset disorder. Iron accumulation begins early in life, and symptoms may appear in childhood. By age 20, decreased or absent secretion of sex hormones is evident. Females usually begin menstruation in a normal manner, but menses stop after a few years. Males may experience delayed puberty or symptoms related to a shortage of sex hormones. If the disorder is untreated, heart disease becomes evident by age 30.The onset of type 3 hemochromatosis is usually intermediate between types 1 and 2. Symptoms of type 3 hemochromatosis generally begin before age 30.  https://ghr.nlm.nih.gov/condition/hereditary-hemochromatosis

Clinical features

Heart failure
MedGen UID:
6749
Concept ID:
C0018801
Disease or Syndrome
Heart failure is a condition in which the heart can't pump enough blood to meet the body's needs. Heart failure does not mean that your heart has stopped or is about to stop working. It means that your heart is not able to pump blood the way it should. It can affect one or both sides of the heart. The weakening of the heart's pumping ability causes. -Blood and fluid to back up into the lungs. -The buildup of fluid in the feet, ankles and legs - called edema. -Tiredness and shortness of breath. Common causes of heart failure are coronary artery disease, high blood pressure and diabetes. It is more common in people who are 65 years old or older, African Americans, people who are overweight, and people who have had a heart attack. Men have a higher rate of heart failure than women. Your doctor will diagnose heart failure by doing a physical exam and heart tests. Treatment includes treating the underlying cause of your heart failure, medicines, and heart transplantation if other treatments fail. NIH: National Heart, Lung, and Blood Institute.
Cardiac conduction abnormalities
MedGen UID:
334259
Concept ID:
C1842820
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.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
Diabetes is a disease in which your blood glucose, or blood sugar, levels are too high. Glucose comes from the foods you eat. Insulin is a hormone that helps the glucose get into your cells to give them energy. With type 1 diabetes, your body does not make insulin. With type 2 diabetes, the more common type, your body does not make or use insulin well. Without enough insulin, the glucose stays in your blood. You can also have prediabetes. This means that your blood sugar is higher than normal but not high enough to be called diabetes. Having prediabetes puts you at a higher risk of getting type 2 diabetes. Over time, having too much glucose in your blood can cause serious problems. It can damage your eyes, kidneys, and nerves. Diabetes can also cause heart disease, stroke and even the need to remove a limb. Pregnant women can also get diabetes, called gestational diabetes. A blood test can show if you have diabetes. Exercise, weight control and sticking to your meal plan can help control your diabetes. You should also monitor your glucose level and take medicine if prescribed. . NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
Hypogonadotropic hypogonadism 7 with or without anosmia
MedGen UID:
82883
Concept ID:
C0271623
Disease or Syndrome
Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is characterized by inappropriately low serum concentrations of the gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in the setting of hypogonadism. IGD is associated with a normal sense of smell (normosmic IGD) in approximately 40% of affected individuals and an impaired sense of smell (Kallmann syndrome [KS]) in approximately 60%. IGD can first be apparent in infancy, adolescence, or adulthood. Infant boys with congenital (i.e., present at birth) IGD often have micropenis and cryptorchidism. Adolescents and adults with IGD have clinical evidence of hypogonadism and incomplete sexual maturation on physical examination. Adult males with IGD tend to have prepubertal testicular volume (i.e., <4 mL), absence of secondary sexual features (e.g., facial and axillary hair growth, deepening of the voice), decreased muscle mass, diminished libido, erectile dysfunction, and infertility. Adult females have little or no breast development and primary amenorrhea. Although skeletal maturation is delayed, the rate of linear growth is usually normal except for the absence of a distinct pubertal growth spurt.
Amenorrhea
MedGen UID:
853709
Concept ID:
C2219717
Sign or Symptom
Absence of menses for an interval of time equivalent to a total of more than (or equal to) 3 previous cycles or 6 months.
Ascites
MedGen UID:
416
Concept ID:
C0003962
Finding
Accumulation of fluid in the peritoneal cavity.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Sign or Symptom
Enlargement of the liver.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Enlargement of the spleen.
Diabetes mellitus
MedGen UID:
8350
Concept ID:
C0011849
Disease or Syndrome
Diabetes is a disease in which your blood glucose, or blood sugar, levels are too high. Glucose comes from the foods you eat. Insulin is a hormone that helps the glucose get into your cells to give them energy. With type 1 diabetes, your body does not make insulin. With type 2 diabetes, the more common type, your body does not make or use insulin well. Without enough insulin, the glucose stays in your blood. You can also have prediabetes. This means that your blood sugar is higher than normal but not high enough to be called diabetes. Having prediabetes puts you at a higher risk of getting type 2 diabetes. Over time, having too much glucose in your blood can cause serious problems. It can damage your eyes, kidneys, and nerves. Diabetes can also cause heart disease, stroke and even the need to remove a limb. Pregnant women can also get diabetes, called gestational diabetes. A blood test can show if you have diabetes. Exercise, weight control and sticking to your meal plan can help control your diabetes. You should also monitor your glucose level and take medicine if prescribed. . NIH: National Institute of Diabetes and Digestive and Kidney Diseases.
Decreased glucose tolerance
MedGen UID:
852424
Concept ID:
C0151671
Finding
An abnormal resistance to glucose, i.e., a reduction in the ability to maintain glucose levels in the blood stream within normal limits following oral or intravenous administration of glucose.
Increased serum iron
MedGen UID:
57739
Concept ID:
C0151900
Finding
Hyperferritinaemia
MedGen UID:
892475
Concept ID:
C3854388
Disease or Syndrome
Abnormal raised concentration of ferritin, a ubiquitous intracellular protein that stores iron, in the blood.

Professional guidelines

PubMed

Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS; American Association for the Study of Liver Diseases.
Hepatology 2011 Jul;54(1):328-43. doi: 10.1002/hep.24330. PMID: 21452290Free PMC Article
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
U.S. Preventive Services Task Force.
Ann Intern Med 2006 Aug 1;145(3):204-8. PMID: 16880462

Recent clinical studies

Etiology

Camacho A, Funck-Brentano T, Simão M, Cancela L, Ottaviani S, Cohen-Solal M, Richette P
PLoS One 2015 Mar 30;10(3):e0122817. 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

Camacho A, Funck-Brentano T, Simão M, Cancela L, Ottaviani S, Cohen-Solal M, Richette P
PLoS One 2015 Mar 30;10(3):e0122817. 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. PMID: 12382200

Clinical prediction guides

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 Jul 21;10(7):e0132852. 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. PMID: 12382200

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