Genetic Disorders of Iron Metabolism
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 overloadIron 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).