Biology:Hypotransferrinemia
Hypotransferrinemia, is an autosomal recessive metabolic disorder in which the body produces not enough transferrin, a plasma protein that transports iron through the blood.[1][2] Once believed to be a synonyme for atransferrinemia (the total absence of transferrin) today’s science is aware of the fact that hypotransferrinemia is a way more common phenotype of mutations in the HFE- und transferrin genes.[3] Hypotransferrinemia is characterized by hemosiderosis mostly in the brain, heart, liver, skin and testicles. The iron damages can lead to brain damage, heart failure and other severe damages and dysfunctions.[4][5] As of 2020 there is still no causal therapy for primary (genetically caused) hypotransferrinemia.
Symptoms and signs
The presentation of this disorder entails brain damage, neurological conditions, heart dysfunctions, and any kind of symptoms that arise on the grounds of iron oxidation within human cells caused by non-transferrin (protein) bound iron (NTBI).[6][7][8][9][10]
Genetics
In terms of genetics of hypotransferrinemia researchers have identified mutations in the TF gene as a probable cause of this genetic disorder in affected people as well as mutations in one of the HFE-genes.[1][11]
Transferrin is a serum transport protein that transports iron to the reticuloendothelial system for utilization and erythropoiesis.[12][13][14] Due to a lack of sufficient transferrin excess iron deposits itself in the brain, heart, liver, skin, testicles and joints causes structural damages.[15][16]
Diagnosis
The diagnosis of hypotransferrinemia is done via the following means to ascertain if an individual has the condition:[1]
- Blood tests for iron, transferrin, transferrin saturation and ferritin
- Physical exam
- Genetic test
Treatment
Other than for hemochromatosis or atransferrinemia there are no treatment options available for people suffering from hypotransferrinemia. Only symptomatic treatments can be tried to improve the consequences caused by the overload with non-transferrin bound iron (NTBI).[17]
See also
- Transferrin
- Ferritin
- HFE (gene)
- Hemochromatosis
- Atransferrinemia
- HFE H63D gene mutation
References
- ↑ 1.0 1.1 1.2 RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Congenital atransferrinemia" (in en). http://www.orpha.net/consor4.01/www/cgi-bin/OC_Exp.php?lng=EN&Expert=1195.
- ↑ "OMIM Entry - # 209300 - ATRANSFERRINEMIA" (in en-us). https://omim.org/entry/209300. Retrieved 19 February 2017.
- ↑ Linda McManus, Richard Mitchell (2014): Pathobiology of Human Disease: A Dynamic Encyclopedia of Disease Mechanisms. San Antonio, Boston, Elsevier Academic Press
- ↑ Marie-Pascale Beaumont-Epinette et al.: Hereditary hypotransferrinemia can lead to elevated transferrin saturation and, when associated to HFE or HAMP mutations, to iron overload. Blood Cells, Molecules, and Diseases. Volume 54, Issue 2, February 2015, Pages 151-154. https://doi.org/10.1016/j.bcmd.2014.11.020
- ↑ Pierre Brissot: Non-transferrin bound iron: A key role in iron overload and iron toxicity. In: Biochimica et Biophysica Acta 1820(3):403-10. August 2011. DOI: 10.1016/j.bbagen.2011.07.014
- ↑ R.C. Hider, Nature of nontransferrin-bound iron, Eur. J. Clin. Invest. 32 (Suppl. 1, 2002) 50–54.
- ↑ Danilo Milardi, Enrico Rizzarelli (2011): Neurodegeneration: Metallostasis and Proteostasis. Chapter 9. Royal Society of Chemistry.
- ↑ Alizadeh BZ, Njajou OT, Millán MR, Hofman A, Breteler MM, van Duijn CM: HFE variants, APOE and Alzheimer’s disease: Findings from the population-based Rotterdam study. In: Neurobiol Aging. 2009 Feb;30(2):330-2.
- ↑ Berlin D, Chong G, Chertkow H, Bergman H, Phillips NA, Schipper HM: Evaluation of HFE (hemochromatosis) mutations as genetic modifiers in sporadic AD and MCI. In: Neurobiol Aging. 2004 Apr;25(4):465-74.
- ↑ P. Brissot, et al., Non-transferrin bound iron: A key role in iron overload and iron toxicity , Biochim. Biophys. Acta (2011), doi:10.1016/j.bbagen.2011.07.014
- ↑ Porto, Graca; de Sousa, Maria (2000). Barton, James C.; Edwards, Corwin Q. (eds.). Variation of hemochromatosis prevalence and genotype in national groups. In: Hemochromatosis: Genetics, pathophysiology, diagnosis and treatment: Cambridge University Press. ISBN:978-0521593809.
- ↑ Bartnikas, Thomas Benedict (1 August 2012). "Known and potential roles of transferrin in iron biology" (in en). BioMetals 25 (4): 677–686. doi:10.1007/s10534-012-9520-3. PMID 22294463.
- ↑ Reference, Genetics Home. "TF gene" (in en). https://ghr.nlm.nih.gov/gene/TF#conditions.
- ↑ "OMIM Entry - * 190000 - TRANSFERRIN; TF" (in en-us). https://omim.org/entry/190000. Retrieved 20 February 2017.
- ↑ Nemeth E, Ganz T (2006). "Regulation of iron metabolism by hepcidin". Annual Review of Nutrition. 26: doi:10.1146/annurev.nutr.26.061505.111303
- ↑ K. Jomova, M. Valko, Advances in metal-induced oxidative stress and human disease, Toxicology 283 (2011) 65–87.
- ↑ Chaim Hershko (2012): Iron Chelation Therapy. Springer Science & Business Media.
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