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Elevated transferrin saturation

MedGen UID:
868498
Concept ID:
C4022892
Finding
HPO: HP:0012463

Definition

An above normal level of saturation of serum transferrin with iron. [from HPO]

Conditions with this feature

Hemochromatosis type 5
MedGen UID:
341982
Concept ID:
C1851316
Disease or Syndrome
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.
Hemochromatosis type 4
MedGen UID:
340044
Concept ID:
C1853733
Disease or Syndrome
Hemochromatosis type 4 (HFE4) is a dominantly inherited iron overload disorder with heterogeneous phenotypic manifestations that can be classified into 2 groups. One group is characterized by an early rise in ferritin (see 134790) levels with low to normal transferrin (190000) saturation and iron accumulation predominantly in macrophages. The other group is similar to classical hemochromatosis, with high transferrin saturation and prominent parenchymal iron loading (summary by De Domenico et al., 2005). For general background information and a discussion of genetic heterogeneity of hereditary hemochromatosis, see 235200.
Hemochromatosis type 3
MedGen UID:
388114
Concept ID:
C1858664
Disease or Syndrome
TFR2-related hereditary hemochromatosis (TFR2-HHC) is characterized by increased intestinal iron absorption resulting in iron accumulation in the liver, heart, pancreas, and endocrine organs. Age of onset is earlier than in HFE-HHC. The majority of individuals present with signs and symptoms of iron overload in the third decade (e.g., weakness, fatigue, abdominal pain, hepatomegaly, arthritis, arthralgia, progressive increase in skin pigmentation). Others present as young adults with nonspecific symptoms and abnormal serum iron studies or as adults with abnormal serum iron studies and signs of organ involvement including cirrhosis, diabetes mellitus, and arthropathy.
Hemochromatosis type 2B
MedGen UID:
356040
Concept ID:
C1865616
Disease or Syndrome
Juvenile hemochromatosis is characterized by onset of severe iron overload occurring typically in the first to third decades of life. Males and females are equally affected. Prominent clinical features include hypogonadotropic hypogonadism, cardiomyopathy, glucose intolerance and diabetes, arthropathy, and liver fibrosis or cirrhosis. Hepatocellular cancer has been reported occasionally. The main cause of death is cardiac disease. If juvenile hemochromatosis is detected early enough and if blood is removed regularly through the process of phlebotomy to achieve iron depletion, morbidity and mortality are greatly reduced.
Severe congenital hypochromic anemia with ringed sideroblasts
MedGen UID:
815250
Concept ID:
C3808920
Disease or Syndrome
STEAP3/TSAP6-related sideroblastic anemia is a very rare severe non-syndromic hypochromic anemia, which is characterized by transfusion-dependent hypochromic, poorly regenerative anemia, iron overload, resembling non-syndromic sideroblastic anemia (see this term) except for increased erythrocyte protoporphyrin levels.
Sideroblastic anemia 2
MedGen UID:
899109
Concept ID:
C4225425
Disease or Syndrome
Ferro-cerebro-cutaneous syndrome
MedGen UID:
1658844
Concept ID:
C4751570
Disease or Syndrome
A rare genetic metabolic liver disease with characteristics of progressive neurodegeneration, cutaneous abnormalities including varying degrees of ichthyosis or seborrheic dermatitis, and systemic iron overload. Patients manifest with infantile-onset seizures, encephalopathy, abnormal eye movements, axial hypotonia with peripheral hypertonia, brisk reflexes, cortical blindness and deafness, myoclonus and hepato/splenomegaly, as well as oral manifestations including microdontia, widely spaced and pointed teeth with delayed eruption and gingival overgrowth.
Iron overload, susceptibility to
MedGen UID:
1814970
Concept ID:
C5703292
Finding
Iron overload (IO) is characterized by the onset of increased systemic iron levels apparent in mid-adulthood. Laboratory studies show increased serum ferritin, normal or high transferrin saturation, increased liver iron content, and inappropriately low or normal levels of hepcidin. Presence of a BMP6 mutation confers susceptibility to the disorder, but additional factors, including alcohol consumption, increased body weight, and possibly HFE gene (613609) variants, may contribute to the severity of the manifestations (Daher et al., 2016; Piubelli et al., 2017).

Professional guidelines

PubMed

European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver
J Hepatol 2022 Aug;77(2):479-502. Epub 2022 Jun 1 doi: 10.1016/j.jhep.2022.03.033. PMID: 35662478
Ellervik C, Tybjaerg-Hansen A, Appleyard M, Ibsen H, Nordestgaard BG
J Intern Med 2010 Sep;268(3):252-64. Epub 2010 Jan 29 doi: 10.1111/j.1365-2796.2010.02217.x. PMID: 20337854
Witte DL, Crosby WH, Edwards CQ, Fairbanks VF, Mitros FA
Clin Chim Acta 1996 Feb 28;245(2):139-200. doi: 10.1016/0009-8981(95)06212-2. PMID: 8867884

Recent clinical studies

Etiology

Kroll DS, McPherson KL, Manza P, Schwandt ML, Shen PH, Goldman D, Diazgranados N, Wang GJ, Wiers CE, Volkow ND
Addict Biol 2022 Mar;27(2):e13144. doi: 10.1111/adb.13144. PMID: 35229939Free PMC Article
Mainous AG 3rd, Wright RU, Hulihan MM, Twal WO, McLaren CE, Diaz VA, McLaren GD, Argraves WS, Grant AM
Biometals 2014 Feb;27(1):135-41. Epub 2013 Dec 15 doi: 10.1007/s10534-013-9693-4. PMID: 24337410Free PMC Article
Crownover BK, Covey CJ
Am Fam Physician 2013 Feb 1;87(3):183-90. PMID: 23418762
Fix OK, Kowdley KV
Minerva Med 2008 Dec;99(6):605-17. PMID: 19034258
Ajioka RS, Kushner JP
Semin Hematol 2002 Oct;39(4):235-41. doi: 10.1053/shem.2002.35634. PMID: 12382198

Diagnosis

European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu; European Association for the Study of the Liver
J Hepatol 2022 Aug;77(2):479-502. Epub 2022 Jun 1 doi: 10.1016/j.jhep.2022.03.033. PMID: 35662478
Datz C, Müller E, Aigner E
Minerva Endocrinol 2017 Jun;42(2):173-183. Epub 2016 Nov 11 doi: 10.23736/S0391-1977.16.02565-7. PMID: 27834478
Gulati V, Harikrishnan P, Palaniswamy C, Aronow WS, Jain D, Frishman WH
Cardiol Rev 2014 Mar-Apr;22(2):56-68. doi: 10.1097/CRD.0b013e3182a67805. PMID: 24503941
Crownover BK, Covey CJ
Am Fam Physician 2013 Feb 1;87(3):183-90. PMID: 23418762
Fix OK, Kowdley KV
Minerva Med 2008 Dec;99(6):605-17. PMID: 19034258

Therapy

Gulati V, Harikrishnan P, Palaniswamy C, Aronow WS, Jain D, Frishman WH
Cardiol Rev 2014 Mar-Apr;22(2):56-68. doi: 10.1097/CRD.0b013e3182a67805. PMID: 24503941
Orban E, Schwab S, Thorand B, Huth C
Diabetes Metab Res Rev 2014 Jul;30(5):372-94. doi: 10.1002/dmrr.2506. PMID: 24327370
Ellervik C, Tybjaerg-Hansen A, Appleyard M, Ibsen H, Nordestgaard BG
J Intern Med 2010 Sep;268(3):252-64. Epub 2010 Jan 29 doi: 10.1111/j.1365-2796.2010.02217.x. PMID: 20337854
Carson KR, Evens AM, Bennett CL, Luminari S
Best Pract Res Clin Haematol 2005;18(3):467-72. doi: 10.1016/j.beha.2005.01.015. PMID: 15792921
Mainous AG 3rd, Wells B, Carek PJ, Gill JM, Geesey ME
Ann Fam Med 2004 Mar-Apr;2(2):139-44. doi: 10.1370/afm.82. PMID: 15083854Free PMC Article

Prognosis

Kroll DS, McPherson KL, Manza P, Schwandt ML, Shen PH, Goldman D, Diazgranados N, Wang GJ, Wiers CE, Volkow ND
Addict Biol 2022 Mar;27(2):e13144. doi: 10.1111/adb.13144. PMID: 35229939Free PMC Article
Datz C, Müller E, Aigner E
Minerva Endocrinol 2017 Jun;42(2):173-183. Epub 2016 Nov 11 doi: 10.23736/S0391-1977.16.02565-7. PMID: 27834478
Gulati V, Harikrishnan P, Palaniswamy C, Aronow WS, Jain D, Frishman WH
Cardiol Rev 2014 Mar-Apr;22(2):56-68. doi: 10.1097/CRD.0b013e3182a67805. PMID: 24503941
Crownover BK, Covey CJ
Am Fam Physician 2013 Feb 1;87(3):183-90. PMID: 23418762
Mainous AG 3rd, Gill JM, Carek PJ
Ann Fam Med 2004 Mar-Apr;2(2):133-8. doi: 10.1370/afm.25. PMID: 15083853Free PMC Article

Clinical prediction guides

Kroll DS, McPherson KL, Manza P, Schwandt ML, Shen PH, Goldman D, Diazgranados N, Wang GJ, Wiers CE, Volkow ND
Addict Biol 2022 Mar;27(2):e13144. doi: 10.1111/adb.13144. PMID: 35229939Free PMC Article
Aigner E, Feldman A, Datz C
Nutrients 2014 Sep 11;6(9):3587-600. doi: 10.3390/nu6093587. PMID: 25215659Free PMC Article
Orban E, Schwab S, Thorand B, Huth C
Diabetes Metab Res Rev 2014 Jul;30(5):372-94. doi: 10.1002/dmrr.2506. PMID: 24327370
Ellervik C, Andersen HU, Tybjærg-Hansen A, Frandsen M, Birgens H, Nordestgaard BG, Mandrup-Poulsen T
Diabetes Care 2013 Sep;36(9):2646-54. Epub 2013 Jun 25 doi: 10.2337/dc12-2032. PMID: 23801727Free PMC Article
Datz C, Felder TK, Niederseer D, Aigner E
Eur J Clin Invest 2013 Feb;43(2):215-24. Epub 2013 Jan 7 doi: 10.1111/eci.12032. PMID: 23289518

Recent systematic reviews

Mayr R, Janecke AR, Schranz M, Griffiths WJ, Vogel W, Pietrangelo A, Zoller H
J Hepatol 2010 Nov;53(5):941-9. Epub 2010 Jul 17 doi: 10.1016/j.jhep.2010.05.016. PMID: 20691492Free PMC Article

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