Growth in Hemochromatosis
Iron is an essential element for all living organisms. It is necessary for the formation of hemoglobin, and there is an increased need for iron generated by growth spurts. Inadequate supplies of iron during growth spurts can result in delayed maturation. Iron overload, however, is also harmful. Excess iron deposition in parenchymal tissue leads to multiple organ dysfunction. Iron overload can be caused by both genetic and nongenetic factors. Since the discovery of HFE mutations, hereditary hemochromatosis has been recognized as a common inherited disorder. HFE-associated hemochromatosis is the most common genetic disorder, especially in populations of Northern European origin. Recently, several important regulators of iron homeostasis have been discovered. Hepcidin is a central player in iron regulation; it directly regulates intestinal iron absorption, and a mutation in the hepcidin-encoding gene leads to rapid iron accumulation. The HFE protein, hemojuvelin, and transferrin receptor 2 are considered to be upstream modulators of hepcidin. Hemochromatosis results in the classic triad of diabetes mellitus, skin pigmentation, and liver cirrhosis. However, clinical manifestations are markedly influenced by several factors such as mutations in hemochromatosis-associated genes, gender, and other underlying diseases. Hemochromatosis is often misdiagnosed and untreated. Family history provides important diagnostic clues, and iron overload is diagnosed by measuring transferrin saturation percentage and serum ferritin levels. However, the physician must be aware that normal infants can have high transferrin saturation percentages and elevated serum ferritin levels. Magnetic resonance imaging is a useful tool for detecting iron deposition in organs. Histological biopsy is not necessary for diagnosis. Frequent phlebotomy can remove iron from parenchymal cells, and iron chelation therapy is useful for selected patients. Dysfunction of some organs is irreversible, however. If untreated, hemochromatosis can cause serious illness and early death; therefore, early diagnosis and appropriate management are critical to prognosis.
KeywordsIron Overload Transferrin Receptor Iron Deposition Serum Ferritin Level Hereditary Hemochromatosis
Bone morphogenic protein
Duodenal cytochrome b-like protein
Divalent metal transporter-1
Heme carrier protein-1
Hyperferritinemia cataract syndrome
Magnetic resonance imaging
Transferrin saturation percentage
The author would like to thank Dr Hisao Ogawa, Dr Seigo Sugiyama, Dr Hiroaki Kawano, and Dr Masafumi Nakayama, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, and Dr Yutaka Kuroda, Department of Community Medicine, Kumamoto University Hospital for their discussion on this manuscript. The author is grateful to Dr Masayoshi Kage, Department of Pathology, Kurume University School of Medicine and Dr Takahisa Yoshida, Section of Pathology, Fukuoka Tokusyukai Hospital for their important contributions. The cooperation of patients and families involved in our study is gratefully acknowledged.
- Adams PC, Reboussin DM, Barton JC, McLaren CE, Eckfeldt JH, McLaren GD, Dawkins FW, Acton RT, Harris EL, Gordeuk VR, Leiendecker-Foster C, Speechley M, Snively BM, Holup JL, Thomson E, Sholinsky P, Hemochromatosis and Iron Overload Screening (HEIRS) Study Research Investigators. Hemochromatosis and iron-overload screening in a racially diverse population. N Engl J Med. 2005;352:1769–78.PubMedCrossRefGoogle Scholar
- ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Eur Heart J. 2008;29:2388–442.Google Scholar
- Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA, Basava A, Dormishian F, Domingo R Jr, Ellis MC, Fullan A, Hinton LM, Jones NL, Kimmel BE, Kronmal GS, Lauer P, Lee VK, Loeb DB, Mapa FA, McClelland E, Meyer NC, Mintier GA, Moeller N, Moore T, Morikang E, Prass CE, Quintana L, Starnes SM, Schatzman RC, Brunke KJ, Drayna DT, Risch NJ, Bacon BR, Wolff RK. A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nat Genet. 1996;13:399–408.Google Scholar
- Ko C, Siddaiah N, Berger J, Gish R, Brandhagen D, Sterling RK, Cotler SJ, Fontana RJ, McCashland TM, Han SH, Gordon FD, Schilsky ML, Kowdley KV. Prevalence of hepatic iron overload and association with hepatocellular cancer in end-stage liver disease: results from the National Hemochromatosis Transplant Registry. Liver Int. 2007;27:1394–401.PubMedCrossRefGoogle Scholar
- Papanikolaou G, Samuels ME, Ludwig EH, MacDonald ML, Franchini PL, Dubé MP, Andres L, MacFarlane J, Sakellaropoulos N, Politou M, Nemeth E, Thompson J, Risler JK, Zaborowska C, Babakaiff R, Radomski CC, Pape TD, Davidas O, Christakis J, Brissot P, Lockitch G, Ganz T, Hayden MR, Goldberg YP. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet. 2004;36:77–82.PubMedCrossRefGoogle Scholar