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Hereditary hemochromatosis(HFE)

MedGen UID:
140272
Concept ID:
C0392514
Disease or Syndrome
Synonym: HFE
SNOMED CT: Idiopathic hemochromatosis (399053004); Primary hemochromatosis (399170009); Hereditary hemochromatosis (35400008); Familial hemochromatosis (35400008)
 
Related genes: HJV, HAMP, SLC40A1, TFR2, HFE, FTH1, BMP2
 
Monarch Initiative: MONDO:0006507
OMIM®: 235200; 608374
OMIM® Phenotypic series: PS235200

Disease characteristics

Excerpted from the GeneReview: HFE-Related Hemochromatosis
HFE-related hemochromatosis (HFE HC) is characterized by increased intestinal iron absorption and increased recycling of iron derived from senescent red blood cells. The phenotypic spectrum of HFE HC includes clinical HFE HC (increased serum ferritin and transferrin saturation and end-organ damage secondary to iron overload), biochemical HFE HC (increased serum ferritin and transferrin saturation without end-organ damage), and non-penetrant HFE HC (neither clinical manifestations of HFE HC nor iron overload are present, although elevated transferrin saturation may occur). Clinical HFE HC is characterized by excessive iron in the liver, pancreas, heart, skin, joints, and anterior pituitary gland. In untreated individuals, early manifestations include weakness, chronic fatigue, abdominal pain, weight loss, arthralgias, and diabetes mellitus. Individuals with HFE HC have an increased risk of cirrhosis when their serum ferritin is higher than 1,000 µg/L. Other findings of severe iron overload include hypogonadism, congestive heart failure, arrhythmias, and progressive increase in skin pigmentation. Clinical HFE HC is more common in males than females. [from GeneReviews]
Authors:
James C Barton  |  Charles J Parker   view full author information

Additional descriptions

From OMIM
Hereditary hemochromatosis (HFE) is an autosomal recessive disorder of iron metabolism wherein the body accumulates excess iron. 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. Removal of excess iron by therapeutic phlebotomy decreases morbidity and mortality if instituted early in the course of the disease. Classic hemochromatosis (HFE) is most often caused by mutation in a gene designated HFE on chromosome 6p22 (summary by Feder et al., 1996). Adams and Barton (2007) reviewed the clinical features, pathophysiology, and management of hemochromatosis. Genetic Heterogeneity of Hemochromatosis At least 4 additional iron overload disorders labeled hemochromatosis have been identified on the basis of clinical, biochemical, and genetic characteristics. Juvenile hemochromatosis, or hemochromatosis type 2 (HFE2), is autosomal recessive and is divided into 2 forms: HFE2A (602390), caused by mutation in the HJV gene (608374) on chromosome 1q21, and HFE2B (613313), caused by mutation in the HAMP gene (606464) on chromosome 19q13. Hemochromatosis type 3 (HFE3; 604250), an autosomal recessive disorder, is caused by mutation in the TFR2 gene (604720) on chromosome 7q22. Hemochromatosis type 4 (HFE4; 606069), an autosomal dominant disorder, is caused by mutation in the SLC40A1 gene (604653) on chromosome 2q32. Hemochromatosis type 5 (HFE5; 615517) is caused by mutation in the FTH1 gene (134770) on chromosome 11q12.  http://www.omim.org/entry/235200
From MedlinePlus Genetics
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 may include extreme tiredness (fatigue), joint pain, abdominal pain, weight loss, and loss of sex drive. As the condition worsens, affected individuals may develop arthritis, liver disease (cirrhosis) or liver cancer, diabetes, heart abnormalities, or skin discoloration. The appearance and severity of symptoms can be affected by environmental and lifestyle factors such as the amount of iron in the diet, alcohol use, and infections.

There are four types of hereditary hemochromatosis, which are classified 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 known as a juvenile-onset disorder because symptoms often begin in childhood. By age 20, iron accumulation causes decreased or absent secretion of sex hormones. Affected females usually begin menstruation normally but menses stop after a few years. Males may experience delayed puberty or symptoms related to a shortage of sex hormones. If type 2 hemochromatosis is untreated, potentially fatal heart disease becomes evident by age 30.

The onset of type 3 hemochromatosis is usually intermediate between types 1 and 2 with symptoms generally beginning before age 30.  https://medlineplus.gov/genetics/condition/hereditary-hemochromatosis

Professional guidelines

PubMed

Kowdley KV, Brown KE, Ahn J, Sundaram V
Am J Gastroenterol 2019 Aug;114(8):1202-1218. doi: 10.14309/ajg.0000000000000315. PMID: 31335359
Kwo PY, Cohen SM, Lim JK
Am J Gastroenterol 2017 Jan;112(1):18-35. Epub 2016 Dec 20 doi: 10.1038/ajg.2016.517. PMID: 27995906
Pietrangelo A
Gastroenterology 2010 Aug;139(2):393-408, 408.e1-2. Epub 2010 Jun 11 doi: 10.1053/j.gastro.2010.06.013. PMID: 20542038

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

Sninsky JA, Shore BM, Lupu GV, Crockett SD
Gastrointest Endosc Clin N Am 2022 Apr;32(2):195-213. Epub 2022 Feb 22 doi: 10.1016/j.giec.2021.12.008. PMID: 35361331
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Am Fam Physician 2021 Sep 1;104(3):263-270. PMID: 34523883
Kowdley KV, Brown KE, Ahn J, Sundaram V
Am J Gastroenterol 2019 Aug;114(8):1202-1218. doi: 10.14309/ajg.0000000000000315. PMID: 31335359
Creighton Mitchell T, McClain DA
Curr Diab Rep 2014;14(5):488. doi: 10.1007/s11892-014-0488-y. PMID: 24682660
Pietrangelo A
Gastroenterology 2010 Aug;139(2):393-408, 408.e1-2. Epub 2010 Jun 11 doi: 10.1053/j.gastro.2010.06.013. PMID: 20542038

Diagnosis

Cabrera E, Crespo G, VanWagner LB
JAMA 2022 Nov 8;328(18):1862-1863. doi: 10.1001/jama.2022.17727. PMID: 36346422
Sninsky JA, Shore BM, Lupu GV, Crockett SD
Gastrointest Endosc Clin N Am 2022 Apr;32(2):195-213. Epub 2022 Feb 22 doi: 10.1016/j.giec.2021.12.008. PMID: 35361331
Kane SF, Roberts C, Paulus R
Am Fam Physician 2021 Sep 1;104(3):263-270. PMID: 34523883
Kowdley KV, Brown KE, Ahn J, Sundaram V
Am J Gastroenterol 2019 Aug;114(8):1202-1218. doi: 10.14309/ajg.0000000000000315. PMID: 31335359
Pietrangelo A
Gastroenterology 2010 Aug;139(2):393-408, 408.e1-2. Epub 2010 Jun 11 doi: 10.1053/j.gastro.2010.06.013. PMID: 20542038

Therapy

Kowdley KV, Brown KE, Ahn J, Sundaram V
Am J Gastroenterol 2019 Aug;114(8):1202-1218. doi: 10.14309/ajg.0000000000000315. PMID: 31335359
Oh CK, Moon Y
Nutrients 2019 May 10;11(5) doi: 10.3390/nu11051047. PMID: 31083351Free PMC Article
Salgia RJ, Brown K
Clin Liver Dis 2015 Feb;19(1):187-98. Epub 2014 Oct 23 doi: 10.1016/j.cld.2014.09.011. PMID: 25454304
Trost LB, Bergfeld WF, Calogeras E
J Am Acad Dermatol 2006 May;54(5):824-44. doi: 10.1016/j.jaad.2005.11.1104. PMID: 16635664
Fattovich G, Stroffolini T, Zagni I, Donato F
Gastroenterology 2004 Nov;127(5 Suppl 1):S35-50. doi: 10.1053/j.gastro.2004.09.014. PMID: 15508101

Prognosis

Sninsky JA, Shore BM, Lupu GV, Crockett SD
Gastrointest Endosc Clin N Am 2022 Apr;32(2):195-213. Epub 2022 Feb 22 doi: 10.1016/j.giec.2021.12.008. PMID: 35361331
Crownover BK, Covey CJ
Am Fam Physician 2013 Feb 1;87(3):183-90. PMID: 23418762
Pietrangelo A
Gastroenterology 2010 Aug;139(2):393-408, 408.e1-2. Epub 2010 Jun 11 doi: 10.1053/j.gastro.2010.06.013. PMID: 20542038
Fattovich G, Stroffolini T, Zagni I, Donato F
Gastroenterology 2004 Nov;127(5 Suppl 1):S35-50. doi: 10.1053/j.gastro.2004.09.014. PMID: 15508101
Knisely AS, Mieli-Vergani G, Whitington PF
Gastroenterol Clin North Am 2003 Sep;32(3):877-89, vi-vii. doi: 10.1016/s0889-8553(03)00050-5. PMID: 14562579

Clinical prediction guides

Roemhild K, von Maltzahn F, Weiskirchen R, Knüchel R, von Stillfried S, Lammers T
Trends Pharmacol Sci 2021 Aug;42(8):640-656. Epub 2021 Jun 2 doi: 10.1016/j.tips.2021.05.001. PMID: 34090703Free PMC Article
Oh RC, Hustead TR, Ali SM, Pantsari MW
Am Fam Physician 2017 Dec 1;96(11):709-715. PMID: 29431403
Parkash O, Akram M
J Coll Physicians Surg Pak 2015 Sep;25(9):644-7. PMID: 26374358
Pietrangelo A
Gastroenterology 2010 Aug;139(2):393-408, 408.e1-2. Epub 2010 Jun 11 doi: 10.1053/j.gastro.2010.06.013. PMID: 20542038
Fattovich G, Stroffolini T, Zagni I, Donato F
Gastroenterology 2004 Nov;127(5 Suppl 1):S35-50. doi: 10.1053/j.gastro.2004.09.014. PMID: 15508101

Recent systematic reviews

Wijarnpreecha K, Aby ES, Panjawatanan P, Kroner PT, Harnois DM, Palmer WC, Ungprasert P
Eur J Gastroenterol Hepatol 2021 Jan;33(1):96-101. doi: 10.1097/MEG.0000000000001704. PMID: 32118852
Kong X, Xie L, Zhu H, Song L, Xing X, Yang W, Chen X
Orphanet J Rare Dis 2019 Jul 8;14(1):171. doi: 10.1186/s13023-019-1097-2. PMID: 31286966Free PMC Article
Tran KT, Coleman HG, McCain RS, Cardwell CR
Nutr Cancer 2019;71(8):1365-1373. Epub 2019 May 2 doi: 10.1080/01635581.2019.1609053. PMID: 31044614
Liu J, Sun B, Yin H, Liu S
Medicine (Baltimore) 2016 Apr;95(14):e3150. doi: 10.1097/MD.0000000000003150. PMID: 27057839Free PMC Article
Whitlock EP, Garlitz BA, Harris EL, Beil TL, Smith PR
Ann Intern Med 2006 Aug 1;145(3):209-23. doi: 10.7326/0003-4819-145-3-200608010-00009. PMID: 16880463

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