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Hemochromatosis type 5(HFE5)

MedGen UID:: 341982
•Concept ID:: C1851316
•: Disease or Syndrome

Synonym:	Iron overload, autosomal dominant
SNOMED CT:	FTH1-associated iron overload (1230310007); Ferritin heavy chain 1-related iron overload (1230310007); FTH1-related iron overload (1230310007); FTH1 (ferritin heavy chain 1) related iron overload (1230310007)
Modes of inheritance:	Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • 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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal dominant inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	FTH1 (11q12.3)

Monarch Initiative:	MONDO:0014225
OMIM®:	615517
Orphanet:	ORPHA247790

Definition

A rare disorder of iron metabolism and transport characterised by elevated serum ferritin levels, increased serum iron, increased transferrin saturation and heavy iron deposition in hepatocytes. Iron deposition has also been indicated in heart and bone marrow, while haematological examination of peripheral blood shows no abnormalities. [from SNOMEDCT_US]

Clinical features

From HPO

Elevated hepatic iron concentration

MedGen UID:: 868497
•Concept ID:: C4022891
•: Finding

An increased level of iron in liver tissues.

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Anemia

MedGen UID:: 1526
•Concept ID:: C0002871
•: Disease or Syndrome

A reduction in erythrocytes volume or hemoglobin concentration.

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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.

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Increased circulating ferritin concentration

MedGen UID:: 69130
•Concept ID:: C0241013
•: Finding

Increased concentration of ferritin in the blood circulation.

See: Feature record | Search on this feature

Elevated transferrin saturation

MedGen UID:: 868498
•Concept ID:: C4022892
•: Finding

An above normal level of saturation of serum transferrin with iron.

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Abnormal circulating copper concentration

MedGen UID:: 892610
•Concept ID:: C4023689
•: Finding

An abnormal concentration of copper.

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Abnormal circulating transferrin concentration

MedGen UID:: 1694121
•Concept ID:: C5139308
•: Finding

Any deviation from the normal concentration of transferrin in the blood circulation.

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Abnormal circulating ceruloplasmin concentration

MedGen UID:: 1726009
•Concept ID:: C5421638
•: Finding

Any deviation of the concentration of ceruloplasmin in the blood from the normal range.

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Abnormality of blood and blood-forming tissues
- Anemia
Abnormality of metabolism/homeostasis
Abnormality of the digestive system
- Elevated hepatic iron concentration

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

Disorder of iron metabolism and transport
- Hemochromatosis type 5

Follow this link to review classifications for Hemochromatosis type 5 in Orphanet.

Professional guidelines

PubMed

Risk of Hepatocellular Carcinoma in Patients with Various HFE Genotypes.

Natarajan Y, Patel P, Chu J, Yu X, Hernaez R, El-Serag H, Kanwal F
Dig Dis Sci 2023 Jan;68(1):312-322. Epub 2022 Jul 5 doi: 10.1007/s10620-022-07602-9. PMID: 35790703

Correlation of genotype and phenotype in 32 patients with hereditary hemochromatosis in China.

Wu L, Zhang W, Li Y, Zhou D, Zhang B, Xu A, Wu Z, Wu L, Li S, Wang X, Zhao X, Wang Q, Li M, Wang Y, You H, Huang J, Ou X, Jia J
Orphanet J Rare Dis 2021 Sep 28;16(1):398. doi: 10.1186/s13023-021-02020-y. PMID: 34583728 Free PMC Article

The evaluation of hyperferritinemia: an updated strategy based on advances in detecting genetic abnormalities.

Aguilar-Martinez P, Schved JF, Brissot P
Am J Gastroenterol 2005 May;100(5):1185-94. doi: 10.1111/j.1572-0241.2005.40998.x. PMID: 15842597

See all (18)

Recent clinical studies

Etiology

Iron homeostasis in mice: does liver lobe matter?

Colucci S, Carvalho Oliveira T, Muckenthaler MU, Marques O
Am J Physiol Gastrointest Liver Physiol 2023 Nov 1;325(5):G453-G457. Epub 2023 Sep 5 doi: 10.1152/ajpgi.00085.2023. PMID: 37667844

Hemochromatosis classification: update and recommendations by the BIOIRON Society.

Girelli D, Busti F, Brissot P, Cabantchik I, Muckenthaler MU, Porto G
Blood 2022 May 19;139(20):3018-3029. doi: 10.1182/blood.2021011338. PMID: 34601591 Free PMC Article

Managing the Unusual Causes of Fetal Anemia.

Maisonneuve E, Ben M'Barek I, Leblanc T, Da Costa L, Friszer S, Pernot F, Thomas P, Castaigne V, Toly N'Dour C, Mailloux A, Cortey A, Jouannic JM
Fetal Diagn Ther 2020;47(2):156-164. Epub 2019 Sep 10 doi: 10.1159/000501554. PMID: 31505487

Prenatal iron exposure and childhood type 1 diabetes.

Størdal K, McArdle HJ, Hayes H, Tapia G, Viken MK, Lund-Blix NA, Haugen M, Joner G, Skrivarhaug T, Mårild K, Njølstad PR, Eggesbø M, Mandal S, Page CM, London SJ, Lie BA, Stene LC
Sci Rep 2018 Jun 13;8(1):9067. doi: 10.1038/s41598-018-27391-4. PMID: 29899542 Free PMC Article

Diabetes and hemochromatosis.

Creighton Mitchell T, McClain DA
Curr Diab Rep 2014;14(5):488. doi: 10.1007/s11892-014-0488-y. PMID: 24682660

See all (124)

Diagnosis

Hereditary hemochromatosis: data from a single center Copenhagen cohort.

Therkildsen R, Dahl EE, Schiødt FV
Scand J Gastroenterol 2022 Aug;57(8):972-977. Epub 2022 Mar 7 doi: 10.1080/00365521.2022.2042591. PMID: 35249441

Hemochromatosis classification: update and recommendations by the BIOIRON Society.

Girelli D, Busti F, Brissot P, Cabantchik I, Muckenthaler MU, Porto G
Blood 2022 May 19;139(20):3018-3029. doi: 10.1182/blood.2021011338. PMID: 34601591 Free PMC Article

Juvenile haemochromatosis.

Griffiths WJH, Besser M, Bowden DJ, Kelly DA
Lancet Child Adolesc Health 2021 Jul;5(7):524-530. Epub 2021 Apr 15 doi: 10.1016/S2352-4642(20)30392-8. PMID: 33861982

Diagnostic morphology: biophysical indicators for iron-driven inflammatory diseases.

Pretorius E, Kell DB
Integr Biol (Camb) 2014 May;6(5):486-510. doi: 10.1039/c4ib00025k. PMID: 24714688

HFE-associated hereditary hemochromatosis.

Alexander J, Kowdley KV
Genet Med 2009 May;11(5):307-13. doi: 10.1097/GIM.0b013e31819d30f2. PMID: 19444013

See all (97)

Therapy

Genetic studies of abdominal MRI data identify genes regulating hepcidin as major determinants of liver iron concentration.

Wilman HR, Parisinos CA, Atabaki-Pasdar N, Kelly M, Thomas EL, Neubauer S; IMI DIRECT Consortium, Mahajan A, Hingorani AD, Patel RS, Hemingway H, Franks PW, Bell JD, Banerjee R, Yaghootkar H
J Hepatol 2019 Sep;71(3):594-602. Epub 2019 Jun 19 doi: 10.1016/j.jhep.2019.05.032. PMID: 31226389 Free PMC Article

Prenatal iron exposure and childhood type 1 diabetes.

Hemochromatosis gene (HFE) polymorphisms and risk of type 2 diabetes mellitus: a meta-analysis.

Rong Y, Bao W, Rong S, Fang M, Wang D, Yao P, Hu FB, Liu L
Am J Epidemiol 2012 Sep 15;176(6):461-72. Epub 2012 Aug 19 doi: 10.1093/aje/kws126. PMID: 22908207

Porphyria cutanea tarda--when skin meets liver.

Frank J, Poblete-Gutiérrez P
Best Pract Res Clin Gastroenterol 2010 Oct;24(5):735-45. doi: 10.1016/j.bpg.2010.07.002. PMID: 20955974

Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy.

Oudit GY, Trivieri MG, Khaper N, Liu PP, Backx PH
J Mol Med (Berl) 2006 May;84(5):349-64. Epub 2006 Apr 8 doi: 10.1007/s00109-005-0029-x. PMID: 16604332 Free PMC Article

See all (34)

Prognosis

HLA-A*03, the hemochromatosis ancestral haplotype, and phenotypes of referred hemochromatosis probands with HFE p.C282Y homozygosity.

Barton JC, Barton JC, Acton RT
Hereditas 2022 Jun 6;159(1):25. doi: 10.1186/s41065-022-00237-w. PMID: 35659379 Free PMC Article

Splicing analysis of SLC40A1 missense variations and contribution to hemochromatosis type 4 phenotypes.

Le Tertre M, Ka C, Raud L, Berlivet I, Gourlaouen I, Richard G, Uguen K, Chen JM, Férec C, Fichou Y, Le Gac G
Blood Cells Mol Dis 2021 Mar;87:102527. Epub 2020 Dec 8 doi: 10.1016/j.bcmd.2020.102527. PMID: 33341511

Managing the Unusual Causes of Fetal Anemia.

Prenatal iron exposure and childhood type 1 diabetes.

Hereditary alpha-1-antitrypsin deficiency and its clinical consequences.

Fregonese L, Stolk J
Orphanet J Rare Dis 2008 Jun 19;3:16. doi: 10.1186/1750-1172-3-16. PMID: 18565211 Free PMC Article

See all (48)

Clinical prediction guides

Iron homeostasis in mice: does liver lobe matter?

Colucci S, Carvalho Oliveira T, Muckenthaler MU, Marques O
Am J Physiol Gastrointest Liver Physiol 2023 Nov 1;325(5):G453-G457. Epub 2023 Sep 5 doi: 10.1152/ajpgi.00085.2023. PMID: 37667844

HLA-A*03, the hemochromatosis ancestral haplotype, and phenotypes of referred hemochromatosis probands with HFE p.C282Y homozygosity.

Barton JC, Barton JC, Acton RT
Hereditas 2022 Jun 6;159(1):25. doi: 10.1186/s41065-022-00237-w. PMID: 35659379 Free PMC Article

Splicing analysis of SLC40A1 missense variations and contribution to hemochromatosis type 4 phenotypes.

Diagnostic morphology: biophysical indicators for iron-driven inflammatory diseases.

Pretorius E, Kell DB
Integr Biol (Camb) 2014 May;6(5):486-510. doi: 10.1039/c4ib00025k. PMID: 24714688

Porphyria cutanea tarda--when skin meets liver.

Frank J, Poblete-Gutiérrez P
Best Pract Res Clin Gastroenterol 2010 Oct;24(5):735-45. doi: 10.1016/j.bpg.2010.07.002. PMID: 20955974

See all (74)