Genetic Disorders of
IRON METABOLISAM
The most common form of genetic iron overload is hereditary hemochromatosis, a condition in which excessive dietary iron is absorbed from the gut (approximately 2-3 times the normal quantity) (1). HFE-associated hemochromatosis is the most common genetic disorder among Caucasians of northern European descent, with approximately 0.3-0.5% being homozygous for the disease (2,3) and 10% being heterozygous (3).
Rare genetic disorders of iron transport, such as hypotransferrinemia, atransferrinemia, and aceruloplasminemia, can also lead to iron overload.
Gradual iron accumulation
Despite the relatively gradual time course of iron accumulation in genetic compared to transfusional iron overload, the clinical manifestations of iron toxicity are strikingly similar. Both groups tend to develop serious hepatic and cardiac manifestations over time.
Iron toxicity develops more gradually in primary iron overload
Iron toxicity develops more gradually in primary iron overload
The rate of onset of clinical manifestations of iron toxicity depends on the rate of iron accumulation. Complications may never develop in heterozygous hemochromatosis; they may take decades to develop in homozygous hemochromatosis; and regularly transfused patients with thalassemia major may experience serious complications within years. Adapted with permission from Olivieri and Brittenham (4).
Email
Print
Serum Ferritin
>1000 mcg/L in HH
Iron overload can be confirmed without
liver biopsy in HFE homozygotes if
serum ferritin is
>1000 mcg/L.
References
- * (1)Cox TM, Peters TJ, Uptake of iron by duodenal biopsy specimens from patients with iron-deficiency anaemia and primary haemochromatosis. Lancet. 1978;1(8056):123-4.
- * (2)Pietrangelo A, Camaschella C, Molecular genetics and control of iron metabolism in hemochromatosis. Haematologica. 1998;83(5):456-61.
- * (3)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 in a racially diverse population. N Engl J Med. 2005; 352(17):1769-78.
- * (4) Olivieri NF, Brittenham GM, Iron-chelating therapy and the treatment of thalassemia. Blood. 1997; 89(3):739-61.