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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.

See: Feature record | Search on this feature

Abnormal circulating copper concentration

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

An abnormal concentration of copper.

See: Feature record | Search on this feature

Abnormal circulating transferrin concentration

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

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

See: Feature record | Search on this feature

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

Genetic testing in the European Union: does economic evaluation matter?

Antoñanzas F, Rodríguez-Ibeas R, Hutter MF, Lorente R, Juárez C, Pinillos M
Eur J Health Econ 2012 Oct;13(5):651-61. Epub 2011 May 20 doi: 10.1007/s10198-011-0319-x. PMID: 21598012

See all (18)

Recent clinical studies

Etiology

Hemochromatosis Gene Mutation in Persons Developing Erythrocytosis on Combined Testosterone and SGLT-2 Inhibitor Therapy.

Schumacher KA, Gosmanov AR
J Investig Med High Impact Case Rep 2022 Jan-Dec;10:23247096221111774. doi: 10.1177/23247096221111774. PMID: 35848311 Free PMC Article

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

Diabetes and hemochromatosis.

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

C282Y-HFE gene variant affects cholesterol metabolism in human neuroblastoma cells.

Ali-Rahmani F, Huang MA, Schengrund CL, Connor JR, Lee SY
PLoS One 2014;9(2):e88724. Epub 2014 Feb 12 doi: 10.1371/journal.pone.0088724. PMID: 24533143 Free PMC Article

Neuromuscular manifestations in hereditary haemochromatosis.

Wouthuis SF, van Deursen CT, te Lintelo MP, Rozeman CA, Beekman R
J Neurol 2010 Sep;257(9):1465-72. Epub 2010 Apr 1 doi: 10.1007/s00415-010-5548-x. PMID: 20358215

See all (124)

Diagnosis

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

C282Y-HFE gene variant affects cholesterol metabolism in human neuroblastoma cells.

Ali-Rahmani F, Huang MA, Schengrund CL, Connor JR, Lee SY
PLoS One 2014;9(2):e88724. Epub 2014 Feb 12 doi: 10.1371/journal.pone.0088724. PMID: 24533143 Free PMC Article

Neuromuscular manifestations in hereditary haemochromatosis.

Wouthuis SF, van Deursen CT, te Lintelo MP, Rozeman CA, Beekman R
J Neurol 2010 Sep;257(9):1465-72. Epub 2010 Apr 1 doi: 10.1007/s00415-010-5548-x. PMID: 20358215

Role of ferritin and ferroportin genes in unexplained hyperferritinaemia.

Cazzola M
Best Pract Res Clin Haematol 2005 Jun;18(2):251-63. doi: 10.1016/j.beha.2004.08.025. PMID: 15737888

See all (97)

Therapy

Hyperferritinemia and diagnosis of type 1 Gaucher disease.

Marchi G, Nascimbeni F, Motta I, Busti F, Carubbi F, Cappellini MD, Pietrangelo A, Corradini E, Piperno A, Girelli D
Am J Hematol 2020 May;95(5):570-576. Epub 2020 Feb 22 doi: 10.1002/ajh.25752. PMID: 32031266

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

A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia.

Bekri S, May A, Cotter PD, Al-Sabah AI, Guo X, Masters GS, Bishop DF
Blood 2003 Jul 15;102(2):698-704. Epub 2003 Mar 27 doi: 10.1182/blood-2002-06-1623. PMID: 12663458

Hereditary juvenile haemochromatosis: a genetically heterogeneous life-threatening iron-storage disease.

Kelly AL, Rhodes DA, Roland JM, Schofield P, Cox TM
QJM 1998 Sep;91(9):607-18. doi: 10.1093/qjmed/91.9.607. PMID: 10024915

Use of subcutaneous deferoxamine in a child with hemochromatosis associated with congenital dyserythropoietic anemia, type I.

Smithson WA, Perrault J
Mayo Clin Proc 1982 May;57(5):322-5. PMID: 7078263

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Prognosis

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

Ferritin concentrations in synovial fluid are higher in osteoarthritis patients with HFE gene mutations (C282Y or H63D).

Carroll GJ, Sharma G, Upadhyay A, Jazayeri JA
Scand J Rheumatol 2010;39(5):413-20. doi: 10.3109/03009741003677449. PMID: 20560808

Neuromuscular manifestations in hereditary haemochromatosis.

Wouthuis SF, van Deursen CT, te Lintelo MP, Rozeman CA, Beekman R
J Neurol 2010 Sep;257(9):1465-72. Epub 2010 Apr 1 doi: 10.1007/s00415-010-5548-x. PMID: 20358215

The biochemical and clinical penetrance of individuals diagnosed with genetic haemochromatosis by predictive genetic testing.

Watkins S, Thorburn D, Joshi N, Neilson M, Joyce T, Spooner R, Cooke A, Mills PR, Morris AJ, Stanley AJ
Eur J Gastroenterol Hepatol 2008 May;20(5):379-83. doi: 10.1097/MEG.0b013e3282f3e708. PMID: 18403938

Survival advantage of the hemochromatosis C282Y mutation.

Weinberg ED
Perspect Biol Med 2008 Winter;51(1):98-102. doi: 10.1353/pbm.2008.0001. PMID: 18192769

See all (48)

Clinical prediction guides

Survival advantage of the hemochromatosis C282Y mutation.

Weinberg ED
Perspect Biol Med 2008 Winter;51(1):98-102. doi: 10.1353/pbm.2008.0001. PMID: 18192769

Ferroportin gene silencing induces iron retention and enhances ferritin synthesis in human macrophages.

Gallí A, Bergamaschi G, Recalde H, Biasiotto G, Santambrogio P, Boggi S, Levi S, Arosio P, Cazzola M
Br J Haematol 2004 Dec;127(5):598-603. doi: 10.1111/j.1365-2141.2004.05238.x. PMID: 15566364

Regulation of transferrin-induced endocytosis by wild-type and C282Y-mutant HFE in transfected HeLa cells.

Schwake L, Henkel AW, Riedel HD, Schlenker T, Both M, Migala A, Hadaschik B, Henfling N, Stremmel W
Am J Physiol Cell Physiol 2002 May;282(5):C973-9. doi: 10.1152/ajpcell.00415.2001. PMID: 11940510

The hemochromatosis gene affects the age of onset of sporadic Alzheimer's disease.

Sampietro M, Caputo L, Casatta A, Meregalli M, Pellagatti A, Tagliabue J, Annoni G, Vergani C
Neurobiol Aging 2001 Jul-Aug;22(4):563-8. doi: 10.1016/s0197-4580(01)00219-6. PMID: 11445256

Ethnic differences in the HFE codon 282 (Cys/Tyr) polymorphism.

Beckman LE, Saha N, Spitsyn V, Van Landeghem G, Beckman L
Hum Hered 1997 Sep-Oct;47(5):263-7. doi: 10.1159/000154422. PMID: 9358014

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Hemochromatosis type 5(HFE5)

Definition

Clinical features

Term Hierarchy

Professional guidelines

PubMed

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Practice guidelines

Molecular resources

Consumer resources

Reviews

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